Pubmed abstracts for Protein-Protein Interaction search result :


Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.65969963
The increased lipid efflux appears to involve a direct interaction between apoA 1 and ABC 1 , because ABC 1 expression substantially increased apoA 1 binding at the cell surface , and chemical cross linking and immunoprecipitation analysis showed that apoA 1 binds directly to ABC 1 . 0.65969963^^^ The studies provide evidence for a direct interaction between ABC 1 and apoA 1 , but not HDL , indicating that free apoA 1 is the metabolic substrate for ABC 1 . 0.63954125^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.65842259
Naturally occurring mutations in the largest extracellular loops of ABCA 1 can disrupt its direct interaction with apolipoprotein A 1 . 0.65842259^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :1.0335299
These results demonstrate that : 1 ) the physical interaction of apoA 1 with ABCA 1 does not depend on membrane phosphatidylcholine or sphingomyelin ; 2 ) the association of apoA 1 with lipids reduces its ability to interact with ABCA 1 ; and 3 ) the lipid translocase activity of ABCA 1 generates alpha LpA 1 like particles . 1.0335299^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.65855592
To explore the functional interactions between apoA 1 and ABCA 1 , we correlated the cross linking properties of several apoA 1 mutants with their ability to promote cholesterol efflux . 0.65855592^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.57058281
Interaction of apoA 1 with ABCA 1 prevents phosphorylation of a sequence rich in proline , glutamic acid , serine and threonine in a cytoplasmic domain of ABCA 1 , resulting in less degradation by calpain proteolysis and increased surface expression of ABCA 1 . 0.57058281^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.54335497
It has been suggested that ABCA 1 interacts preferentially with lipid poor apolipoprotein A 1 ( apoA 1 ) . 0.54335497^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.64738184
The complex and beneficial interactions between apoA 1 and ABCA 1 seem to be pivotal for cholesterol efflux . 0.64738184^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.52643007
We also showed the interaction between apoA 1 and ABCA 1 in ER and Golgi fractions . 0.52643007^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :1.0684865
To address this issue , we characterized the lipid particles released when J 774 mouse macrophages and human skin fibroblasts in which ABCA 1 is activated are incubated with human apoA 1 . 1.0684865^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.57661733
Existing data indicate that functional interactions between apoA 1 and ABCA 1 are necessary for the initial lipidation of apoA 1 . 0.57661733^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.63489929
Particularly , three questions remain controversial and are discussed in this review : ( 1 ) Do apoA 1 and HDL directly interact with ABCA 1 and ABCG 1 , respectively . ( 2 ) Does cholesterol efflux involve retroendocytosis of apoA 1 or HDL . ( 3 ) Which lipids are directly transported by ABCA 1 and ABCG 1 ? . 0.63489929^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
ABC 1 is expressed on the plasma membrane and the Golgi complex , mediates apo AI associated export of cholesterol and phospholipids from the cell , and is regulated by cholesterol flux . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
In contrast , the mRNA levels of the potential regulatory proteins of the HDL level such as apoA 1 , apoE , LCAT , PLTP , SRB 1 and ABC 1 did not change with probucol . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
Consistent with the reduction in cholesterol and phospholipid efflux in Tangier fibroblasts , downregulation of ABC 1 expression by IFN gamma also resulted in reduced phosphatidylcholine and sphingomyelin efflux to apolipoprotein A 1 . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
Release of membrane phospholipids and cholesterol to apo AI , the protein core of the cholesterol shuttling high density lipoprotein ( HDL ) particle , is also ABC 1 dependent . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
Treatment of macrophages with 8 bromo cAMP ( cAMP ) resulted in a 4 . 1 fold increase in ABC 1 mRNA level and also increased cholesterol efflux to HDL ( 2 . 2 fold ) and apoA 1 ( 5 . 5 fold ) . ^^^ Transfection of a murine ABC 1 cDNA into 293 cells led to a 2 . 3 fold increase of cholesterol efflux to apoA 1 , whereas co transfection of SR BI with ABC 1 blocked this increase in cholesterol efflux . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
Endogenous ABC 1 gene expression in RAW cells and apolipoprotein A 1 mediated cholesterol efflux were also upregulated by both receptor ligands . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
Smooth muscle cells ( SMC ) expressed high levels of ABC 1 transporter mRNA , and glyburide dependent PL and FC efflux to apolipoprotein A 1 ( apo A 1 ) , the major protein of high density lipoprotein . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
This review gives an overview of the genes regulating these mechanisms , such as those encoding apolipoprotein AI , lecithin : cholesterol acyltransferase ( LCAT ) , scavenger receptor B 1 ( SR BI ) , and the ATP binding cassette transporter 1 ( ABC 1 ) , and the potential to exploit them to develop gene based therapeutic approaches to increase the level or function of HDL . . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
Expression of WT macrophage ABCA 1 in ABC 1 ( / ) mice resulted in a small but significant increase in apoA 1 levels starting 2 weeks after transplantation . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
This review will focus on : ( a ) the ability of apoE to direct cholesterol efflux mechanisms with the aid of apoA 1 and the ATP binding cassette transporter 1 ( ABC 1 ) ; ( b ) the ability of apoE to prevent platelet aggregation by facilitating the production of endogenous nitric oxide ( NO ) ; ( c ) the ability of apoE to inhibit the proliferation of T lymphocytes by internalization of the IL 2 receptor ; and ( d ) the ability of apoE to inhibit proliferation of endothelial cells by out competing growth factors for interaction with cell surface heparan sulfate proteoglycans ( HSPG ' s ) . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
ATP binding cassette transporter 1 ( ABCA 1 ) is known to facilitate the release of cellular phospholipids and cholesterol from the plasma membrane to apoA 1 and high density lipoprotein . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
Identification of mutations in the ATP binding cassette transporter 1 ( ABCA 1 ) gene in patients with Tangier disease , who exhibit reduced HDL cholesterol and apolipoprotein A 1 concentrations and premature coronary atherosclerosis , has led us to hypothesise that ABCA 1 could play a key role in the onset of premature CHD in FH . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
ATP binding cassette transporter 1 ( ABCA 1 ) , the defective transporter in Tangier disease , binds and promotes cellular cholesterol and phospholipid efflux to apolipoprotein 1 ( apoA 1 ) . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
The effects of in vivo modulation of HDL phospholipid ( PL ) on scavenger receptor class BI ( SR BI ) and ATP binding cassette transporter 1 ( ABCA 1 ) mediated efflux were examined by overexpressing either endothelial lipase ( EL ) or phosphatidylserine phospholipase ( PS PLA 1 ) in human apolipoprotein A 1 ( apoA 1 ) transgenic mice . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
The ATP binding cassette transporter 1 ( ABCA 1 ) is a trans membrane peptide that is involved in the lipidification of ApoA 1 . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
Mutations in ABCA 1 cause Tangier disease , a severe HDL deficiency syndrome characterized by a rapid turnover of plasma apolipoprotein A 1 , accumulation of sterol in tissue macrophages , and prevalent atherosclerosis . ^^^ This implies that lipidation of apolipoprotein A 1 by the ABCA 1 pathway is required for generating HDL particles and clearing sterol from macrophages . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
Treatment of RAW 264 macrophages with 8 bromo cAMP caused parallel increases in apoA 1 mediated cholesterol efflux , ABCA 1 mRNA and protein levels , incorporation of ABCA 1 into the plasma membrane , and binding of apoA 1 to cell surface ABCA 1 . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
Identification of mutations in the ATP binding cassette transporter ( ABCA 1 ) gene in patients with Tangier disease , who exhibit reduced HDL cholesterol ( HDL C ) and apolipoprotein A 1 ( apoA 1 ) levels and premature coronary atherosclerosis , has led to the hypothesis that common polymorphisms in the ABCA 1 gene could determine HDL C and apoA 1 levels and the risk of coronary atherosclerosis in the general population . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
ABCA 1 , the ATP binding cassette protein mutated in Tangier disease , mediates the efflux of excess cellular sterol to apoA 1 and thereby the formation of high density lipoprotein . ^^^ Studies of the localization and trafficking of ABCA 1 GFP in the presence of brefeldin A or monensin , agents known to block intracellular vesicular trafficking , as well as apoA 1 mediated cellular lipid efflux , showed that : ( 1 ) ABCA 1 functions in lipid efflux at the cell surface , and ( 2 ) delivery of ABCA 1 to lysosomes for degradation may serve as a mechanism to modulate its surface expression . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
Human ABCA 1 BAC transgenic mice show increased high density lipoprotein cholesterol and ApoAI dependent efflux stimulated by an internal promoter containing liver 10 receptor response elements in intron 1 . ^^^ By using BAC transgenic mice , we have shown that increased human ABCA 1 protein expression results in a significant increase in cholesterol efflux in different tissues and marked elevation in high density lipoprotein ( HDL ) cholesterol levels associated with increases in apoAI and apoAII . ^^^ An internal promoter in human intron 1 containing liver 10 response elements is functional in vivo and directly contributes to regulation of the human ABCA 1 gene in multiple tissues and to raised HDL cholesterol , apoAI , and apoAII levels . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
ABCA 1 transgene expression delayed 125I apoA 1 catabolism in both liver and kidney , leading to increased plasma apoA 1 levels , but had no effect on apoB secretion after infusion of Triton WR 1339 . ^^^ These studies show that steady state overexpression of ABCA 1 in vivo ( a ) raises plasma apoB levels without altering apoB secretion and ( b ) raises plasma HDL C and apoA 1 levels , facilitating hepatic reverse cholesterol transport and biliary cholesterol excretion . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
Here we show that secretion of alpha TOH from cultured cells is mediated in part by ABCA 1 , an ATP binding cassette protein that transports cellular cholesterol and phospholipids to lipid poor high density lipoprotein ( HDL ) apolipoproteins such as apoA 1 . ^^^ Treatment of human fibroblasts and murine RAW 264 macrophages with cholesterol and / or 8 bromo cyclic AMP , which induces ABCA 1 expression , enhanced apoA 1 mediated alpha TOH efflux . ^^^ ApoA 1 lacked the ability to remove alpha TOH from Tangier disease fibroblasts that have a nonfunctional ABCA 1 . ^^^ BHK cells that lack an active ABCA 1 pathway markedly increased secretion of alpha TOH to apoA 1 when forced to express ABCA 1 . ^^^ Exposing apoA 1 to ABCA 1 expressing cells did not enhance its ability to remove alpha TOH from cells lacking ABCA 1 , consistent with this transporter participating directly in the translocation of alpha TOH to apolipoproteins . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
We hypothesize that competitive binding to ABCA 1 may explain the decreased ApoA 1 mediated efflux from fibroblasts . . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
Recently , ATP binding cassette transporter A 1 ( ABCA 1 ) , the defective molecule in Tangier disease , has been shown to stimulate phospholipid and cholesterol efflux to apolipoprotein A 1 ( apoA 1 ) ; however , little is known concerning the cellular cholesterol pools that act as the source of cholesterol for ABCA 1 mediated efflux . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
Addition of potential lipid substrates or lipid acceptors ( apolipoprotein A 1 ) did not modify the ATPase activity or nucleotide occlusion by ABCA 1 . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
Recently , it was demonstrated that pioglitazone is also an agonist of PPAR alpha , which plays a central role in lipid metabolism through enhancing the synthesis of apo AI , apo AII and reverse cholesterol transporters , such as fatty acid transporter molecules , and SR B 1 and ABCA 1 reverse cholesterol transport receptors . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
The ATP binding cassette transporter ABCA 1 mediates cholesterol transport from tissue macrophages to apoA 1 , the major high density lipoprotein protein component . ^^^ This was accompanied by a reduction in the membrane content of ABCA 1 and a decrease in apoA 1 binding to whole cells and to ABCA 1 . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
Induction of ABCA 1 with cAMP , however , did increase sterol efflux to exogenously added apoA 1 from both cell types . ^^^ Inhibitors of ABCA 1 activity significantly reduced ( by 40 % to 50 % ) sterol efflux from both J774E ( + ) and J774E ( ) cells treated with cAMP and apoA 1 . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
Thus , PDE 4 inhibitors cause parallel increases in cAMP levels , ABCA 1 expression and apoA 1 mediated cholesterol efflux . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
Using a sensitive real time fluorescent PCR assay , ABCA 1 mRNA levels were induced by approximately 50 70 fold following 8Br cAMP treatment of the RAW 264 murine macrophage cell line , concomitant with the induction of cholesterol efflux to apoAI and HDL . ^^^ These data demonstrate that ABCA 1 is necessary for the cAMP induced lipid efflux to both apoAI and HDL . . ^^^ Stably transfected ABCA 1 antisense cell line has decreased ABCA 1 mRNA and cAMP induced cholesterol efflux to apolipoprotein AI and HDL . ^^^ A stably transfected ABCA 1 antisense cDNA cell line was created , which led to approximately 50 70 % reductions in ABCA 1 mRNA levels in basal and 8Br cAMP treated cells , and diminished to the same extent the 8Br cAMP mediated efflux of cholesterol to apolipoprotein AI and HDL . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
The presence of more ABCA 1 and cholesterol in the plasma membrane results in a 2 fold increase in the level of specific binding of apoA 1 to the cells with no change in binding affinity . ^^^ Overall , it is clear that enrichment of fibroblasts with unesterified cholesterol enhances efflux of cholesterol and PL to apoA 1 because of three effects , 1 ) increased PC biosynthesis , 2 ) increased PC transport via ABCA 1 , and 3 ) increased cholesterol in the plasma membrane . . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
There were no differences between lipid free apoA 1 ( Milano , ) apoA 1 ( Paris ) , and apoA 1 ( WT ) in mediating the efflux of cholesterol from macrophages , indicating that the cysteine variants interacted normally with the ABCA 1 efflux pathway . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
Incubating non transfected RAW with increasing amounts of acetyl LDL caused a parallel accumulation of cholesterol , whereas 7 alphaRAW cells displayed a complete resistance to cholesterol accumulation . 7 alphaRAW cells displayed increased expression of both ABCA 1 mRNA ( 3 . 1 fold , P < 0 . 001 ) and ABCG 1 mRNA ( 2 . 2 fold , P < 0 . 01 ) , whereas the expression of scavenger receptor class A mRNA was unchanged . 7 alphaRAW cells also displayed small but significant increases in the rate of efflux of [ ( 3 ) H ] cholesterol to both delipidated apolipoprotein A 1 and to HDL . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
ABCA 1 implicated in apo AI mediated lipid efflux and CDC 42 were partially localized in Lubrol but not in Triton detergent resistant membranes . ( 4 ) Apo AI preferentially depleted cholesterol and choline phospholipids from Lubrol rafts , whereas HDL 3 additionally decreased the cholesterol content of Triton rafts . ^^^ In fibroblasts , neither ABCA 1 nor CDC 42 was found in Lubrol rafts , and both apo AI and HDL 3 reduced the lipid content in Lubrol as well as in Triton detergent resistant membranes . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
The pulse label study demonstrated that apoA 1 retarded degradation of ABCA 1 . ^^^ The effects of apoA 1 and ALLN were additive for the increase of ABCA 1 , and the apoA 1 mediated cellular lipid release was enhanced by ALLN . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
Cholesterol loading together with 8 bromo cAMP treatment , which increased ABCA 1 expression , led to a significant increase in cholesterol efflux with apolipoprotein A 1 ( apoA 1 ) as the acceptor . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
These studies establish a novel binding site for apoA 1 on the macrophage ECM that may function together with ABCA 1 in promoting cholesterol efflux . . ^^^ Trypsin sensitive and lipid containing sites of the macrophage extracellular matrix bind apolipoprotein A 1 and participate in ABCA 1 dependent cholesterol efflux . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
Linkage analyses showed that this major gene was not located in chromosomal regions that contain six candidate genes whose protein products are important to HDL metabolism ( LCAT , CETP , APOA 1 , APOE , ABCA 1 , LIPC ) . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
Recent studies of Tangier disease have shown that the ATP binding cassette transporter A 1 ( ABCA 1 ) / apolipoprotein A 1 ( apoA 1 ) interaction is critical for high density lipoprotein particle formation , apoA 1 integrity , and proper reverse cholesterol transport . ^^^ It has been suggested that amphipathic helices of apoA 1 bind to a lipid domain created by the ABCA 1 transporter . ^^^ Alternatively , apoA 1 may bind directly to ABCA 1 itself . ^^^ To better understand this interaction , we created several truncation mutants of apoA 1 and then followed up with more specific point mutants and helix translocation mutants to identify and characterize the locations of apoA 1 required for ABCA 1 mediated cholesterol efflux . ^^^ The role of apolipoprotein A 1 helix 10 in apolipoprotein mediated cholesterol efflux via the ATP binding cassette transporter ABCA 1 . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
The mechanism by which ABCA 1 phosphorylation affected ApoA 1 dependent phospholipid efflux did not involve either alterations in ApoA 1 binding or changes in ABCA 1 protein stability . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
We identified that , in addition to scavenger receptor class B , type 1 ( SR BI ) , pBCEC express ABCA 1 and apolipoprotein A 1 ( apoA 1 ) mRNA and protein . ^^^ Studies on the regulation of ABCA 1 by the liver 10 receptor agonist 24 ( S ) OH cholesterol revealed increased ABCA 1 expression and apoA 1 dependent [ 3H ] cholesterol efflux from pBCEC . ^^^ Basolateral pretreatment with 24 ( S ) OH cholesterol enhanced apoA 1 dependent basolateral cholesterol efflux up to 2 fold along with the induction of ABCA 1 at the basolateral membrane . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
We therefore investigated the effect of testosterone on the gene expression of apolipoprotein A 1 ( apoA 1 ) , hepatic lipase ( HL ) , scavenger receptor B 1 ( SR BI ) , and the ATP binding cassette transporter A 1 ( ABCA 1 ) , all of which are important regulators of HDL metabolism . ^^^ Testosterone had no effect on the expression of apoA 1 in HepG 2 cells and ABCA 1 in either HepG 2 cells or macrophages . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
Recombinant expression of a dominant negative form of FADD or the C terminus of ABCA 1 in the human hepatoma cell line HepG 2 markedly reduced the transfer of phospholipids to apoA 1 . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
ABCA 1 on the cell surface and in endosomes plays an essential role in the cell mediated lipidation of apoA 1 to form nascent HDL . ^^^ Consistent with localization of ABCA 1 at the basolateral ( vascular ) cell surface , expression of ABCA 1 GFP stimulated apoA 1 mediated efflux of WIF B cell cholesterol into the culture medium . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
Here we provide evidence that 1 ) lipid effluxes require both flip of membrane lipids and binding of apolipoproteins to the cell surface , 2 ) apolipoprotein A 1 binding depends on structural determinants on ABCA 1 , and 3 ) phospholipid effluxes can be modulated by engineered mutations on the structural determinants identified on ABCA1 . . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
ATP binding cassette transporter A 1 ( ABCA 1 ) plays a crucial role in apoA 1 lipidation , a key step in reverse cholesterol transport . cAMP induces apoA 1 binding activity and promotes cellular cholesterol efflux . ^^^ Taken together , these findings provide evidence for a link between the cAMP / PKA dependent pathway , ABCA 1 phosphorylation , and apoA 1 mediated cellular cholesterol efflux . . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
The ABCA 1 transporter and ApoA 1 : obligate or facultative partners . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
ABCA 1 , a member of the ATP binding cassette family , mediates the efflux of cellular lipids to free apolipoproteins , mainly apoA 1 . ^^^ The C terminal domain of apoA 1 is clearly involved in ABCA 1 driven lipid efflux . ^^^ The C terminal domain of apolipoprotein A 1 is involved in ABCA 1 driven phospholipid and cholesterol efflux . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
Liver 10 receptor / retinoid 10 receptor ( LXR / RXR ) transcription factors have been found to induce a number of genes involved in the regulation of cellular cholesterol efflux , including the ATP binding cassette transporter A 1 ( ABCA 1 ) , which mediates the active efflux of cellular cholesterol and phospholipids to extracellular acceptors , such as apolipoprotein A 1 ( apoA 1 ) . ^^^ In Chinese hamster ovary ( CHO ) cells with moderate stable overexpression of SCD 1 , cholesterol efflux to apoA 1 was inhibited by 73 % , whereas phospholipid efflux and ABCA 1 protein levels were unchanged . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
Since hepatic ABCA 1 expression was also suggested to contribute to the bulk HDL levels , regulation of the ABCA 1 under conditions of high or low levels of HDL were investigated in mice expressing normal or elevated levels of apoAI . ^^^ To study whether HDL levels correlate with the ABCA 1 expression , wild type ( WT ) and the apoAI transgenic ( A 1 Tg ) mice were fed high fat ( HF ) diet with or without cholic acid ( CA ) for 3 weeks . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
The central helices of ApoA 1 can promote ATP binding cassette transporter A 1 ( ABCA 1 ) mediated lipid efflux . ^^^ The findings suggest that although the central helices of apoA 1 alone can promote ABCA 1 mediated lipid efflux , residues 220 231 are necessary to allow functional interactions between the full length apoA 1 and ABCA 1 that are required for lipid efflux and HDL biogenesis . . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
A PEST sequence in ABCA 1 regulates degradation by calpain protease and stabilization of ABCA 1 by apoA 1 . ^^^ ABCA 1 , the defective molecule in Tangier disease , mediates the efflux of phospholipids and cholesterol from cells to apoA 1 , reversing foam cell formation . ^^^ In an apparent positive feedback loop , apoA 1 binds ABCA 1 , promotes lipid efflux , inhibits calpain degradation , and leads to increased levels of ABCA 1 . ^^^ ApoA 1 infusion also increases ABCA 1 in vivo . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
The pathways of hepatic intra and peri cellular lipidation of apolipoprotein A 1 ( apoA 1 ) were studied by infecting primary mouse hepatocytes from either apoA 1 deficient or ABCA 1 deficient mice with a recombinant adenovirus expressing the human apoA 1 ( hapoA 1 ) cDNA ( endo apoA 1 ) or incubating the hepatocytes with exogenously added hapoA 1 ( exo apoA 1 ) and examining the hapoA 1 containing lipoproteins formed . ^^^ With primary hepatocytes from ABCA 1 deficient mice , the expression and net secretion of adenoviral generated endogenous apoA 1 was unchanged compared with control mice , but ( 3 ) H phospholipids associated with endo apoA 1 and exo apoA 1 decreased by 63 and 25 % , respectively . ^^^ Hepatocyte expression of ABCA 1 is central to the lipidation of newly synthesized apoA 1 but also contributes to the lipidation of exogenous apoA 1 . ^^^ The lipidation by hepatocytes of human apolipoprotein A 1 occurs by both ABCA 1 dependent and independent pathways . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
Functionally , the increased ABCA 1 expression caused by these ligands was followed by elevated apoA 1 and apoE specific cholesterol efflux in neurons and glia . ^^^ In non neuronal and neuronal cells overexpressing a human Swedish variant of amyloid precursor protein , 22R hydroxycholesterol and 9 cis retinoic acid induced ABCA 1 expression and increased apoA 1 mediated cholesterol efflux consequently decreasing cellular cholesterol content . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
Importantly , enhanced vesicular transport in response to apoAI is absent in Tangier fibroblasts , a cell type with deficient cholesterol efflux due to functional ABCA 1 mutations . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
Unlike apoA 1 , L 37pA and D 37pA were also capable , although at a reduced rate , of causing lipid efflux independent of ABCA 1 from control cells , Tangier disease cells , and paraformaldehyde fixed ABCA 1 cells . ^^^ In addition , unlike apoA 1 , synthetic peptides can also efflux lipid by a passive , energy independent pathway that does not involve ABCA 1 but does depend upon their lipid affinity . . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
Hepatic ABCA 1 expression in C57Bl / 6 mice ( n = 15 ) raised baseline levels of TC , PL , FC , HDL C , apoE , and apoA 1 by 150 300 % ( P < 0 . 05 all ) . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
Activation of PPARgamma with the agonist prostaglandin J 2 ( 10 micro M ) and of PPARalpha with either bezafibrate ( 100 micro M ) or Wy 14643 ( 100 micro M ) both increased LXRalpha and ABCA 1 gene expression also and enhanced apoA 1 mediated cholesterol efflux from lipid loaded cells , even in the presence of IL 1beta . ^^^ IL 1beta was shown to inhibit ( 3 ) H cholesterol efflux from HMC and increase total intracellular cholesterol concentration , probably as a result of reduced expression of the adenosine triphosphate ( ATP ) binding cassette A 1 ( ABCA 1 ) , a transporter protein involved in apolipoprotein A 1 ( apo A 1 ) mediated lipid efflux . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
The phenotype of the ABCA 1 deficient mouse parallels the phenotype observed in human Tangier disease , including substantial reductions in both apolipoprotein B and apolipoprotein AI with confounding affects on atherosclerosis . . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
ABCA 1 overexpression also increased cholesterol esterification , which was prevented by addition of apoA 1 , suggesting that some of the cell surface cholesterol not removed by apolipoproteins is transported to the intracellular esterifying enzyme acyl CoA : cholesterol acyltransferase . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
ABCA 1 and non ABCA 1 mediated efflux was studied by using apolipoprotein A 1 ( apoA 1 ) , HDL , and methyl beta cyclodextrin as acceptors . ^^^ Efflux to apoA 1 was decreased in four patients ( 4 / 88 , 4 . 5 % ) , and in all cases , a mutation in the ABCA 1 gene was found . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
ABCA 1 plays a crucial role in active apolipoprotein A 1 ( apoA 1 ) lipidation , a key step in reverse cholesterol transport . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
ApoA 1 , the major apolipoprotein component of HDL , promotes ABCA 1 mediated cholesterol and phospholipid efflux , probably by directly binding to ABCA 1 . ^^^ ApoA 1 and apoE stabilize ABCA 1 in a novel mode of regulation by decreasing PEST sequence mediated calpain proteolysis . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
Lipid efflux onto apolipoprotein A 1 ( apoA 1 ) , which depends on ABCA 1 , was comparable in adipocytes and preadipocytes , demonstrating a differential regulation of ABCA 1 mRNA and cholesterol efflux . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
Therefore , GBEC synthesize apoA 1 and E and efflux cholesterol using ABCA 1 and non ABCA 1 mediated pathways . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
To determine whether the Niemann Pick C 1 protein alters the expression and activity of ABCA 1 , we determined the ability of apolipoprotein A 1 ( apoA 1 ) to deplete pools of cellular cholesterol and phospholipids in human fibroblasts derived from NPC1+ / + , NPC1+ / , and NPC 1 / subjects . ^^^ Consistent with impaired ABCA 1 dependent lipid mobilization to apoA 1 for HDL particle formation , we demonstrate for the first time decreased plasma HDL cholesterol levels in 17 of 21 ( 81 % ) NPC 1 / subjects studied . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
Recent data suggest that potentially important targets for upregulating HDL in humans include upregulators of ABCA 1 and APOA 1 ( e . g . peroxisome proliferator activated receptor and liver 10 receptor agonists ) and downregulators of CETP ( e . g . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
ApoA 1 , LCAT enzyme , ABCA 1 and cholesterol ester transfer protein are involved in RCT . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
To test this hypothesis , plasma from Abca 1 ( / ) mice was incubated with CHO cells that are known to express high levels of ABCA 1 with the intent of restoring the flux of phospholipid and cholesterol onto apoAI . ^^^ Taken together , these observations suggest that ABCA 1 is necessary for the adequate lipidation of apoAI , which enables the interaction with LCAT and subsequent maturation . . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
Phosphorylation of a pest sequence in ABCA 1 promotes calpain degradation and is reversed by ApoA 1 . ^^^ We recently showed that ABCA 1 proteolysis by calpain was dependent on a PEST sequence in the cytoplasmic region of ABCA 1 and was reversed by apoA 1 interaction with ABCA 1 . ^^^ The ABCA 1 T1286A / T1305A mutant was not degraded by calpain and was not further stabilized upon apoA 1 treatment . ^^^ In conclusion , we propose a mechanism of regulation of ABCA 1 cell surface expression and function in which the interaction with apoA 1 results in dephosphorylation of the ABCA 1 PEST sequence and thereby inhibits calpain degradation leading to an increase of ABCA 1 cell surface expression . . ^^^ ATP binding cassette transporter A 1 ( ABCA 1 ) , the defective molecule in Tangier disease , mediates the apoAI dependent efflux of excess cholesterol from cells . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
We found that cell lines expressing ABCA 1 displayed 2 3 fold increases in cholesterol efflux to apoA 1 . ^^^ These data suggest that ceramide may increase the plasma membrane content of ABCA 1 , leading to increased apoA 1 binding and cholesterol efflux . . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
Stimulation of ABCA 1 in rat type 2 cells by 9cRA + 22 OH resulted in a four or fivefold enhancement of efflux of radioactive phospholipid or cholesterol , respectively , from the pneumocytes to apolipoprotein AI ( apo AI ) , whereas cAMP ( 0 . 3 mM ) had no effect . ^^^ ABCA 1 mediated lipid efflux to apo AI was independent of the surfactant secretion pathway , inasmuch as upregulation of ABCA 1 resulted in a reduction of secretagogue stimulated surfactant phospholipid release . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
To address this issue , we monitored efflux to apoA 1 of phosphatidylcholine ( PC ) , sphingomyelin ( SM ) , and unesterified ( free ) cholesterol ( FC ) from J 774 macrophages , in which ABCA 1 is up regulated , and investigated the nature of the particles formed . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
Elevated levels of intracellular cholesterol stimulate the liver 10 receptor pathway , enhancing the expression of ABCA 1 , which increases intracellular trafficking of excess cholesterol to the cell surface for interaction with lipid poor apolipoprotein A 1 to form nascent HDL . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
Surprisingly , ABCA 1 FC efflux was twice as high to sera from the apoA 1 / / apoE / or apoE / mice compared with wild type mice , and this activity correlated with serum apoA 4 . ^^^ Immunodepletion of apoA 4 from apoA 1 / / apoE / serum abolished ABCA 1 FC efflux , indicating that apoAI 5 serves as a potent acceptor for FC efflux via ABCA 1 . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
Protein kinase C ( PKC ) inhibitors suppressed both ABCA 1 stabilization and cellular lipid release mediated by apolipoprotein A 1 ( apoA 1 ) but not ABCA 1 increase by calpain inhibitors . ^^^ The increase of ABCA 1 and the cellular lipid release by apoA 1 were both suppressed by a phosphatidylcholine phospholipase C ( PC PLC ) inhibitor but not by the inhibitors of phosphatidylinositol PLC and phosphatidylinositol 3 kinase . ^^^ A protein phosphatase inhibitor further enhanced the ABCA 1 increase by apoA 1 . ^^^ Biochemical and microscopic evidence indicated that apoA 1 activated PKC alpha , and phosphorylation of ABCA 1 was directly demonstrated by apoA 1 via PKC . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
Overexpression of ABCA 1 dramatically increased binding of both PLTP and apoA 1 to common sites on the cell surface . ^^^ Both PLTP and apoA 1 were covalently cross linked to ABCA 1 , each protein blocked cross linking of the other , and both PLTP and apoA 1 stabilized ABCA 1 protein . ^^^ These results are consistent with PLTP and apoA 1 binding to ABCA 1 at the same or closely related sites . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
ABCA 1 , the mutant molecule in Tangier Disease , mediates efflux of cellular cholesterol to apoA 1 and is induced by liver 10 receptor ( LXR ) / retinoid 10 receptor ( RXR ) transcription factors . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
Cholesterol efflux , an important mechanism by which high density lipoproteins ( HDL ) protect against atherosclerosis , is initiated by docking of apolipoprotein A 1 ( apoA 1 ) , a major HDL protein , to specific binding sites followed by activation of ATP binding cassette transporter A 1 ( ABCA 1 ) and translocation of cholesterol from intracellular compartments to the exofacial monolayer of the plasma membrane where it is accessible to HDL . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
Time dependent release of cholesterol and phospholipid by apolipoprotein A ( apoA ) 1 was parallel both with ABCA 1 and with ABCA 7 when highly expressed in HEK 293 cells , but dose dependent profiles of lipid release on apoA 1 and apoA 2 were somewhat different between ABCA 1 and ABCA 7 . ^^^ Expression of ABCA 1 GFP and apoA 1 mediated lipid release were enhanced in parallel by phorbol 12 myristate 13 acetate ( PMA ) in 293 / 2c cells . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
The cDNA underwent PCR amplification for the following genes : apolipoprotein A 1 ( ApoAI ) , apolipoprotein E ( ApoE ) , ATP binding cassette A 1 ( ABCA 1 ) , liver 10 receptor alpha ( LXRalpha ) and farnesoid 10 receptor ( FXR ) . ^^^ The incubation with cholesterol micelles stimulated both LXR and FXR expression that was accompanied by an increased expression of ABCA 1 and ApoAI genes ( 1 . 4 and 1 . 5 fold , respectively ) and halved the APOE expression . ^^^ The effect on ABCA 1 and ApoAI expression was even stronger ( 5 . 7 and 2 . 6 fold , respectively ) with beta sitosterol containing micelles . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
Apolipoproteins , such as apolipoprotein A 1 ( apoA 1 ) , can stimulate cholesterol efflux from cells expressing the ATP binding cassette transporter A 1 ( ABCA 1 ) . ^^^ All seven proteins stimulated lipid efflux and inhibited the cross linking of apoA 1 to ABCA 1 . ^^^ Cross linking of apoA 1 to ABCA 1 was saturable and occurred at high affinity ( Kd of 7 . 0 + / 1 . 9 nM ) , as was cross linking of apoA 2 . ^^^ After binding to ABCA 1 , apoA 1 rapidly dissociated ( half life of 25 min ) from the complex and was released back into the medium . ^^^ A mutant form of ABCA 1 ( W590S ) that avidly binds apoA 1 but fails to promote cholesterol efflux released apoA 1 with similar kinetics but without transfer of cholesterol to apoA 1 . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
However , changes in the plasma cholesterol concentration or loss of function of ATP binding cassette AI transporter ( ABCA 1 ) , scavenger receptor class B , type 1 ( SR BI ) , low density lipoprotein receptor ( LDLR ) , APOE or APOAI had no effect on sterol turnover in the brain . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
Cytotoxic cellular cholesterol is selectively removed by apoA 1 via ABCA 1 . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
In conclusion , we demonstrated for the first time that the ABCA 1 expressing J 774 cell system is responsive to the percent of apo AI present in human serum as pre beta HDL . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
ATP binding cassette transporter A 1 ( ABCA 1 ) mediates transport of cellular cholesterol and phospholipids to high density lipoprotein ( HDL ) apolipoproteins , such as apoA 1 . ^^^ The protein kinase A ( PKA ) inhibitor H 89 , the TK inhibitor genistein , and the JAK 2 inhibitor AG 490 suppressed apoA 1 mediated cholesterol and phospholipid efflux from ABCA 1 expressing cells without altering the membrane ABCA 1 content . ^^^ Whereas PKA inhibition had no effect on apoA 1 binding to cells or to ABCA 1 , TK and JAK 2 inhibition greatly reduced these activities . ^^^ Mutant cells lacking JAK 2 had a severely impaired apoA 1 mediated cholesterol and phospholipid efflux and apoA 1 binding despite normal ABCA 1 protein levels and near normal cholesterol translocase activity . ^^^ Acute incubation of ABCA 1 expressing cells with apoA 1 had no effect on ABCA 1 phosphorylation but stimulated JAK 2 autophosphorylation . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
Adenosine triphosphate ( ATP ) binding cassette transporter A 1 ( ABCA 1 ) mediates the efflux of cholesterol to apolipoprotein A 1 , a process necessary for high density lipoprotein ( HDL ) formation and reverse cholesterol transport . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
ABCA 1 protein in THP 1 and WT 38 was stabilized against proteolytic degradation by apoA 1 , apoA 2 , and apoE and by all the peptides tested except for L3D37pA , and ABCA 1 phosphorylation closely correlated with its stabilization . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
Along with a dramatic induction of ABCA 1 cholesterol transporter expression , these ligands effectively mediate cholesterol efflux in both CCF STTG 1 cells and mouse astrocytes in the presence or absence of apolipoprotein AI ( apoAI ) . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
The mechanism of action of ABCA 1 is still unclear , but requires the transfer of phospholipid and cholesterol to apolipoprotein A 1 bound by or close to the transporter . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
ATP binding cassette transporter A 1 ( ABCA 1 ) plays an important role in apolipoprotein AI ( apoAI ) mediated cholesterol efflux from peripheral cells . ^^^ The mild changes in ABCA 1 activity due to genomic variation might be associated with interindividual variations in serum high density lipoprotein cholesterol ( HDL C ) and apoAI levels , or primary hypoalphalipoproteinemia in the general population . ^^^ Associations between serum high density lipoprotein cholesterol or apolipoprotein AI levels and common genetic variants of the ABCA 1 gene in Japanese school aged children . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
In depth haplotype analysis of ABCA 1 gene polymorphisms in relation to plasma ApoA 1 levels and myocardial infarction . ^^^ Twenty six polymorphisms of the ABCA 1 gene were genotyped and tested for association with plasma levels of ApoA 1 and myocardial infarction ( MI ) in the ECTIM study . ^^^ CONCLUSIONS : ABCA 1 gene polymorphisms but not haplotypes are involved in the variability of plasma ApoA 1 and the susceptibility to coronary artery disease . . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
We evaluated the association between the ABCA 1 genotype and HDL C level adjusted not only for standard factors , but also for genetic factors including ApoA 1 and ApoE genotypes . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
The liver 10 receptor / retinoid 10 receptor ( LXR / RXR ) regulated gene ABCA 1 effluxes cellular cholesterol and phospholipid to apolipoprotein A 1 ( apoA 1 ) , which is the rate limiting step in high density lipoprotein synthesis . ^^^ However , Sertoli TM 4 cells lack ABCA 1 , and TM 4 cells or primary Sertoli cells cultured from ABCA 1 ( / ) mice both fail to efflux cholesterol to apoA 1 . ^^^ Expression of exogenous ABCA 1 restores apoA 1 dependent cholesterol efflux in Sertoli TM 4 cells . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
The ABCA 1 flippase activity , apolipoprotein AI and AII binding , and cellular phospholipid and cholesterol efflux were enhanced by mutations preventing CK 2 phosphorylation of the threonine and serine residues . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
Lack of ABCA 1 in humans and mice causes abnormal lipidation and increased catabolism of HDL , resulting in very low plasma apoA 1 , apoA 2 , and HDL . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
Deficiency of ABCA 1 results in lack of circulating HDL and greatly reduced levels of apoA 1 . ^^^ Here we demonstrate that glial ABCA 1 is required for cholesterol efflux to apoA 1 and plays a key role in facilitating cholesterol efflux to apoE , which is the major apolipoprotein in the brain . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
The oligomeric structure of ABCA 1 transporter and its function related to the biogenesis of nascent apoA 1 containing particles ( LpA 1 ) were investigated . ^^^ Interestingly , apoA 1 was found to be associated with both dimeric and tetrameric , but not monomeric , forms of ABCA 1 . ^^^ Neither apoA 1 nor lipid molecules did affect ABCA 1 oligomerization . ^^^ Subsequent isolation of LpA 1 followed by cross linking revealed the presence of four and eight apoA 1 molecules per particle , whereas apoA 1 incubated with ABCA 1 mutant ( Q597R ) cells was unable to form such particles and remained in the monomeric form . ^^^ These results demonstrate that : 1 ) ABCA 1 exists as an oligomeric complex ; and 2 ) ABCA 1 oligomerization was independent of apoA 1 binding and lipid molecules . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
Pharmacological and genetic inactivation of ACAT enhanced the apoA 1 mediated cholesterol release through upregulation of ABCA 1 and through cholesterol enrichment in the HDL generated . ^^^ In L 929 cells , the PKC activation caused an increase in apoA 1 mediated cholesterol release without detectable change in phospholipid release and in ABCA 1 expression . ^^^ These results indicate that apoA 1 mobilizes intracellular cholesterol for the ABCA 1 mediated release from the compartment that is under the control of ACAT . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
We sequenced three candidate genes ( ABCA 1 , APOA 1 , and LCAT ) that cause Mendelian forms of low HDL C levels in individuals from a population based study . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
The mutant lipid free apoA 1 had normal capacity to promote ATP binding cassette transporter A 1 ( ABCA 1 ) dependent cholesterol efflux . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
The ABCA 1 transporter regulates intracellular cholesterol levels in the liver and in peripheral cells by effluxing excess cholesterol to lipid poor apoA 1 to form nascent HDL , which is converted to mature alpha HDL by esterification of cholesterol to cholesteryl esters ( CE ) by lecithin cholesterol acyltransferase . ^^^ The hepatic ABCA 1 transporter and apoA 1 are major determinants of levels of plasma alpha HDL cholesterol as well as poorly lipidated apoA 1 , which interact with ABCA 1 transporters on peripheral cells in the process of reverse cholesterol transport . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
The stimulation of cellular cholesterol and phospholipid efflux by apolipoprotein A 1 is mediated by the activity of the ATP binding cassette transporter A 1 ( ABCA 1 ) . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
In contrast to apoA 1 , SAA also removed lipid without ABCA 1 ; cholesterol efflux from control cells to SAA was 10 fold higher than for apoA 1 . ^^^ In summary , SAA can act as a lipid acceptor for ABCA 1 , but unlike apoA 1 , it can also efflux lipid without ABCA 1 , by most likely a detergent like extraction process . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
ATP binding cassette A 1 ( ABCA 1 ) is responsible in vivo for the formation of HDL by promoting the lipidation of apoprotein A 1 ( apoA 1 ) via cholesterol and phospholipid efflux from the liver . ^^^ In both basal and ABCA 1 expressing cells pitavastatin 0 . 1 50microM induced a dose dependent increase in cholesterol efflux to apoA 1 ; this effect was reversed by mevalonate or geranyl geraniol . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
Cyclosporin A traps ABCA 1 at the plasma membrane and inhibits ABCA 1 mediated lipid efflux to apolipoprotein A 1 . ^^^ OBJECTIVE : ABCA 1 mediates cellular cholesterol and phospholipid efflux to apolipoprotein A 1 and other apolipoprotein acceptors . ^^^ Using the RAW264 . 7 mouse macrophage cell line , in which ABCA 1 and its associated cholesterol efflux activity are inducible by cAMP analogues , cyclosporin A inhibition of cholesterol efflux to apolipoprotein A 1 was rapidly reversible after its removal from the culture media , implying that ABCA 1 levels were not drastically reduced by cyclosporin A . ^^^ Despite the increase in cell surface ABCA 1 , cyclosporin A decreased apolipoprotein A 1 uptake , resecretion , and degradation in RAW cells . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
Influence of ApoA 1 structure on the ABCA 1 mediated efflux of cellular lipids . ^^^ To address this issue , we used a series of apoA 1 mutants to examine the contributions of various domains in the molecule to ABCA 1 mediated FC and PL efflux from mouse J 774 macrophages and human skin fibroblasts . ^^^ These results indicate that ABCA 1 mediated lipid efflux is relatively insensitive to the organization of the apoA 1 N terminal helix bundle domain . ^^^ In the first step , apoA 1 binds to ABCA 1 and hydrophobic alpha helices in the C terminal domain of apoA 1 insert into the region of the perturbed PL bilayer created by the PL transport activity of ABCA 1 , thereby allowing the second step of lipidation of apoA 1 and formation of nascent high density lipoprotein particles to occur . . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
The ATP binding cassette transporter A 1 ( ABCA 1 ) facilitates the cellular release of cholesterol and choline phospholipids to apolipoprotein A 1 ( apoA 1 ) and several studies indicate that vesicular transport is associated with ABCA 1 function . ^^^ Silencing of syntaxin 13 by small interfering RNA ( siRNA ) led to reduced ABCA 1 protein levels and hence to a significant decrease in apoA 1 dependent choline phospholipid efflux . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
Further study revealed that pitavastatin increased ABCA 1 mRNA in HMG CoA reductase dependent manner and that Rho and Rho kinase inhibitor ( C3T and Y 27632 ) increased apoA 1 production in the HepG 2 cells . ^^^ These results suggest that pitavastatin efficiently increases apoA 1 in the culture medium of HepG 2 cells by promoting apoA 1 production through inhibition of HMG CoA reductase and suppression of Rho activity and by protecting apoA 1 from catabolism through ABCA 1 induction and lipidation of apoA I . . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
Consistent with the inhibitory effect on ABCA 1 translocation to the plasma membrane , probucol reduced cell surface specific [ 125I ] labeled apolipoprotein AI binding . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
Probucol , an ABCA 1 inactivator , inhibited these reactions , as well as the reversible binding of apoA 1 to HepG 2 . ^^^ Primary cultured hepatocytes of ABCA 1 deficient mice also lacked HDL production regardless of the presence of exogenous apoA 1 . ^^^ HepG 2 cells secreted apoA 1 into the medium even when ABCA 1 was inactivated by probucol , but it was all in a free form as HDL production was inhibited . ^^^ We conclude that the main mechanism for HDL assembly by endogenous apoA 1 in HepG 2 cells is an autocrine like reaction in which apoA 1 is secreted and then interacts with cellular ABCA 1 to generate HDL . . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
ABCA 7 is homologous to ABCA 1 and has recently been shown in cell culture to bind apolipoprotein A 1 ( apoA 1 ) and to promote the efflux of phospholipids . ^^^ Moreover , in ABCA 1 knockout macrophages , there was no detectable apoA 1 stimulated phospholipid efflux , inconsistent with a residual role of ABCA 7 . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
In this process , the ABC transporter A 1 ( ABCA 1 ) protein controls the efflux of intracellular cholesterol to apoAI , the major apolipoprotein of HDL . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
The multivariate model included 512 men with coronary artery disease from the REGRESS study who were completely genotyped for eight polymorphisms selected in the univariate procedure ( ie , APOA 1 G ( 75 ) A , ABCA 1 C ( 477 ) T , ABCA 1 G1051A , APOC 3 T3206G , APOE Arg158Cys , LIPC C ( 514 ) T , LPL Asn291Ser and LPL Ser447Stop ) . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
Similarly , macrophage loading with LPC ( by either adding LPC , or PON 1 or phospholipase A ( 2 ) ) significantly increased apolipoprotein A 1 ( apoA 1 ) mediated cholesterol efflux by 104 , 65 and 56 % , respectively , in ABCA 1 overexpressing macrophages . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
Fortuitously , we were able to directly compare carotid intima media thickness data of substantial numbers of individuals with mutations in either apolipoprotein A 1 ( apoA 1 ) , ATP binding cassette AI ( ABCA 1 ) , lecithin : cholesterol acyltransferase ( LCAT ) or cholesteryl ester transfer protein . ^^^ These data show that carriers of an apoA 1 mutation exhibit the most pronounced accelerated atherosclerosis compared with those carrying mutations in ABCA 1 and LCAT . ^^^ SUMMARY : Intima media thickness studies have provided evidence that hypoalphalipoproteinemia due to mutations in apoA 1 , ABCA 1 , and LCAT is associated with increased progression of atherosclerosis . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
The liver is the major site of both apolipoprotein A 1 ( apoA 1 ) synthesis and ATP binding cassette transporter A 1 ( ABCA 1 ) expression . ^^^ Here , we compare the lipidation with cholesterol and phospholipid of newly synthesized human apoA 1 ( hapoA 1 ) using adenoviral vector mediated endogenous expression or exogenously added hapoA 1 in wild type and ABCA 1 null hepatocytes . ^^^ ABCA 1 deficiency decreased apoA 1 phospholipidation by 80 % , but acquisition of de novo synthesized and exogenous cholesterol only decreased by 40 60 % . ^^^ The transfer of de novo synthesized cholesterol to apoA 1 was decreased at all time points , but that of exogenously delivered cholesterol was independent of ABCA 1 activity at the early time points . ^^^ Progesterone does not affect apoA 1 synthesis or its lipidation but inhibited the early phase of apoA 1 cholesterol lipidation in both wild type and ABCA 1 null hepatocytes . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
Addition of mevalonate , GGPP or farnesyl pyrophosphate completely blocked the statin induced increase in ABCA 1 expression and apoAI mediated cholesterol efflux . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
Targeted inactivation of hepatic Abca 1 causes profound hypoalphalipoproteinemia and kidney hypercatabolism of apoA 1 . ^^^ ABCA 1 controls the rate limiting step in HDL particle assembly by mediating efflux of cholesterol and phospholipid from cells to lipid free apoA 1 , which forms nascent HDL particles . ^^^ In vivo catabolism of HDL apoA 1 from wild type mice or human lipid free apoA 1 was 2 fold higher in Abca 1 ( L / L ) mice compared with controls due to a 2 fold increase in the catabolism of apoA 1 by the kidney , with no change in liver catabolism . ^^^ Furthermore , hepatic , but not extrahepatic , Abca 1 is critical in maintaining the circulation of mature HDL particles by direct lipidation of hepatic lipid poor apoA 1 , slowing its catabolism by the kidney and prolonging its plasma residence time . . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
Fast protein liquid chromatography analysis of plasma revealed that hepatic ABCA 1 protein reduction was associated with an approximately 40 % decrease of HDL cholesterol and a reduction of HDL associated apolipoprotein A 1 and E . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
MPO , expressed in foam cell macrophages , was recently shown to oxidize the ApoA 1 component of HDL , impairing ABCA 1 mediated cholesterol efflux . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
Cholesterol efflux to apoA 1 was significantly reduced ( 30 % to 40 % ; P < 0 . 001 ) in ACAT 1 / peritoneal macrophages compared with ACAT1+ / + controls regardless of apoE expression . 2KO macrophages had a 3 to 4 fold increase in ABCA 1 message levels but decreased ABCA 1 protein levels relative to ACAT1+ / + macrophages . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
ApoA 1 mediated cholesterol efflux via ABCA 1 ( ATP binding cassette transporter A 1 ) is a key regulator of cellular cholesterol balance . ^^^ PDMP was found to up regulate ABCA 1 mRNA and protein expression , thereby identifying a contributing mechanism for the observed acceleration of cholesterol efflux to apoA 1 . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
Here , we show that incubation of exogenous apolipoprotein A 1 ( apoA 1 ) with fibroblasts , CaCo 2 , or CHO overexpressing ABCA 1 cells generates only alpha nascent apolipoprotein A 1 containing particles ( alpha LpA 1 ) with diameters of 8 20 nm , whereas human umbilical vein endothelial cells and ABCA 1 mutant ( Q597R ) cells were unable to form such particles . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
ABCA 1 has been established to be required for the efflux of cholesterol and phospholipids to apolipoproteins such as apoA 1 . ^^^ In the present work , we found exofacial exposure of endogenous phosphatidylserine in the absence of apoA 1 to be enhanced in ABCA 1 GFP expressing MDCKII and HeLa cells compared with control cells . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
The ATP binding cassette transporters , ABCA 1 and ABCG 1 , are major players in mediating cellular efflux of phospholipids and cholesterol to apoA 1 containing lipoproteins including prebeta HDL and alphaHDL and thereby exert important antiatherogenic properties . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
ATP binding cassette transporter A 1 ( ABCA 1 ) promotes the efflux of cellular cholesterol and phospholipids to apoA 1 . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
Treating cells with glycolaldehyde ( GA ) and glyoxal ( GO ) strongly inhibited ABCA 1 dependent transport of cholesterol from cells to apoA 1 , while methylglyoxal had little effect . ^^^ GA and GO destabilized ABCA 1 and nearly abolished its binding of apoA 1 , indicating that these carbonyls directly modified ABCA 1 . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
HDLs in apoA 1 transgenic Abca 1 knockout mice are remodeled normally in plasma but are hypercatabolized by the kidney . ^^^ To determine the relationship between ABCA 1 expression and HDL catabolism , we investigated intravascular remodeling , plasma clearance , and organ specific uptake of HDL in mice expressing the human apolipoprotein A 1 ( apoA 1 ) transgene in the Abca 1 knockout background . ^^^ We also observed 2 fold greater hepatic expression of ABCA 1 protein in hA 1 ( Tg ) mice compared with nontransgenic mice , suggesting that overexpression of human apoA 1 stabilized hepatic ABCA 1 protein in vivo . ^^^ We conclude that ABCA 1 is not required for in vivo remodeling of small HDLs to larger HDL subfractions and that the hypercatabolism of normal HDL particles in knockout mice is attributable to a selective catabolism of HDL apoA 1 by the kidney . . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
Finally , we show that cholesterol efflux to HDL specifically requires ABCG 1 , whereas efflux to apoA 1 requires ABCA 1 . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
Our objective was to evaluate the associations of individual apolipoprotein A 1 ( apoA 1 ) containing HDL subpopulation levels with ABCA 1 and scavenger receptor class B type 1 ( SR BI ) mediated cellular cholesterol efflux . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
When added to cells together , SAA and HDL exerted a synergistic effect in promoting ABCA 1 dependent efflux , suggesting that SAA may remodel HDL in a manner that releases apoA 1 or other efficient ABCA 1 ligands from HDL . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
The pX transgenic mice exhibited elevated mRNA levels of ACAT 1 , and ABCG 5 in the small intestine compared with their littermates , and furthermore , apoA 1 , ABCA 1 , ABCG 5 , ACAT 1 , and ACAT 2 mRNAs were induced more easily by a cholesterol enriched diet in pX transgenic mice than their littermates . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
Compared with LA apoA I+ / + mice , serum from LA apoA 1 / mice had a significantly reduced capacity to function as an acceptor of ABCA 1 and SR BI mediated cellular cholesterol efflux , and also had markedly reduced lecithin cholesterol acyltransferase activity . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
The current model of ABCA 1 functionality is then explained based on studies on a topological model , subcellular localization , apoA 1 dependence of HDL formation , functional defects of Tangier disease mutants , and ATP hydrolysis of purified ABCA 1 . ^^^ ABCA 1 is supposed to function as a transporter of lipids as well as a receptor for apoA 1 . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
These studies have identified several potential new targets , including nuclear receptors , ABCA 1 interactive proteins and apolipoprotein A 1 mimetics , which could be promising tools for raising HDL levels and improving the pharmacological treatment of cardiovascular disease . . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
Inhibition of beta 1 syntrophin decreased ABCA 1 protein levels , whereas overexpression of beta 1 syntrophin increased ABCA 1 cell surface expression and stimulated efflux to apolipoprotein A 1 . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
Mutations in human ABCA 1 cause severe HDL deficiencies characterized by the virtual absence of apoA 1 and HDL and prevalent atherosclerosis . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
Apolipoprotein A 1 ( apoA 1 ) interactions with ABCA 1 expressing cells elicit several responses , including removing cellular lipids , stabilizing ABCA 1 protein , and activating Janus kinase 2 ( JAK 2 ) . ^^^ Peptides containing one amphipathic helix of L or D amino acids ( 2F , D 2F , or 4F ) and a peptide containing two helices ( 37pA ) all promoted ABCA 1 dependent cholesterol efflux , competed for apoA 1 binding to ABCA 1 expressing cells , blocked covalent cross linking of apoA 1 to ABCA 1 , and inhibited ABCA 1 degradation . 37pA was cross linked to ABCA 1 , confirming the direct binding of amphipathic helices to ABCA 1 . 2F , 4F , 37pA , and D 37pA all stimulated JAK 2 autophosphorylation . ^^^ In contrast , apoA 1 and peptides stabilized ABCA 1 protein even in the absence of an active JAK 2 , implying that this process is independent of JAK 2 and lipid efflux promoting binding of amphipathic helices to ABCA 1 . ^^^ Apolipoprotein A 1 ( apoA 1 ) interactions with ABCA 1 expressing cells elicit several responses , including removing cellular lipids , stabilizing ABCA 1 protein , and activating Janus kinase 2 ( JAK 2 ) . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
Furthermore , serum samples that induce larger changes in ACAT activity contain increased levels of HDL particles that preferentially interact with ABCA 1 and that these particles accumulate in the serum of patients because of low activity of ABCA 1 in vivo preventing or limiting the extent of apoA 1 lipidation . . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
A critical part of RCT is cholesterol efflux , in which accumulated cholesterol is removed from macrophages in the subintima of the vessel wall by ATP binding membrane cassette transporter A 1 ( ABCA 1 ) or by other mechanisms , including passive diffusion , scavenger receptor B 1 ( SR B 1 ) , caveolins and sterol 27 hydroxylase , and collected by HDL and apoA 1 . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
ABCA 1 upregulation by 8 ( 4 chlorophenylthio ) adenosine 3 ' : 5 ' cyclic monophosphate ( cpt cAMP ) or 22 ( R ) hydroxycholesterol ( 22 OH ) and 9 cis retinoic acid ( 9cRA ) increased the efflux to apo AI of cellular sterols derived from AcLDL , but not of those from OxLDL . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
Monogenic high density lipoprotein ( HDL ) deficiency , because of defects in the genes of apolipoprotein A 1 ( apoA 1 ) , adenosine triphosphate binding cassette transporter A 1 ( ABCA 1 ) or lecithin : cholesterol acyltransferase ( LCAT ) , can be assumed in patients with HDL cholesterol levels below the fifth percentile within a given population . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
In contrast , cholesterol enrichment of glia failed to increase ABCA 1 expression , although ABCG 1 expression and cholesterol efflux to apoA 1 were increased . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
ABCA 1 and ABCG 1 synergize to mediate cholesterol export to apoA 1 . ^^^ Most importantly , acceptors for ABCG 1 mediated cholesterol export could be generated from incubation of cells with lipid free apoA 1 through the action of ABCA 1 alone . ^^^ CONCLUSIONS : These results indicate a synergistic relationship between ABCA 1 and ABCG 1 in peripheral tissues , where ABCA 1 lipidates any lipid poor / free apoA 1 to generate nascent or pre beta HDL . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
Through this action , there is an increase in the transcription of some genes related to lipid metabolism , such as LLP , APOAI , APOAII , ABCA 1 , as well as decrease in the expression of APOCIII , and many other actions . . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
ABCA 1 serves as a binding partner for apoA 1 , but its participation in apoA 1 induced signaling remains uncertain . ^^^ ApoA 1 induced signaling was abrogated by glyburide , an inhibitor of the ABC transporter family , and in fibroblasts from patients with Tangier disease , which do not express ABCA 1 . ^^^ Conversely , induction of ABCA 1 expression with the liver 10 receptor agonist , T 0901317 , and the retinoid 10 receptor agonist , R 0264456 , potentiated apoA 1 induced signaling . ^^^ We further found that Cdc 42 coimmunoprecipitates with ABCA 1 in ABCA 1 GFP expressing HEK 293 cells exposed to apoA 1 but not in cells expressing ABCA 1 mutants . ^^^ We conclude that ABCA 1 transduces signals from apoA 1 by complexing and activating Cdc 42 and downstream kinases and , therefore , acts as a full apoA 1 receptor . . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
Peritoneal macrophages isolated from the ABCA 1 BAC > LDLr / chimeras exhibited a 60 % ( P=0 . 0006 ) increase in cholesterol efflux to apolipoprotein AI . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
Macrophage cholesterol uptake induces ATP binding cassette ( ABC ) transporter ABCA 1 promoting cholesterol efflux to apolipoprotein A 1 and reducing atherosclerosis . ^^^ We show that TNFalpha induces ABCA 1 mRNA and protein in control and cholesterol loaded macrophages and enhances cholesterol efflux to apolipoprotein A 1 . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
Lysine modification by reductive methylation did not alter apoAI ' s net charge , secondary or tertiary structure as observed by circular dichroism and trytophan fluorescence , respectively , or have much impact on lipid binding or ABCA 1 dependent cholesterol acceptor activity . ^^^ The dose dependent acetoacetylation of an increasing proportion of apoAI lysine residues demonstrated that cholesterol acceptor activity was more sensitive to this modification than lipid binding activity , suggesting that apoAI lysine positive charges play an important role in ABCA 1 mediated lipid efflux beyond the role needed to maintain alpha helical content and lipid binding activity . . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
We previously reported that Tyr 192 is the major site that is chlorinated in apolipoprotein A 1 ( apoA 1 ) , the chief protein in HDL , and that chlorinated apoA 1 loses its ability to promote cholesterol efflux from cells by the ATP binding cassette transporter A 1 ( ABCA 1 ) pathway . ^^^ However , the pathways that promote the chlorination of specific Tyr residues in apoA 1 are controversial , and the mechanism for MPO mediated loss of ABCA 1 dependent cholesterol efflux of apoA 1 is unclear . ^^^ Thus , a combination of Tyr 192 chlorination and methionine oxidation is necessary for depriving apoA 1 of its ABCA 1 dependent cholesterol transport activity . ^^^ Myeloperoxidase impairs ABCA 1 dependent cholesterol efflux through methionine oxidation and site specific tyrosine chlorination of apolipoprotein A 1 . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
Apolipoprotein A 1 binds to ABCA 1 and cellular cholesterol and phospholipids , mainly phosphatidylcholine , are loaded onto apoA 1 to form pre beta high density lipoprotein ( HDL ) . ^^^ Glibenclamide suppressed ABCA 1 ATPase , suggesting that it inhibits apoA 1 dependent cellular cholesterol efflux by suppressing ABCA 1 ATPase activity . ^^^ Apolipoprotein A 1 binds to ABCA 1 and cellular cholesterol and phospholipids , mainly phosphatidylcholine , are loaded onto apoA 1 to form pre beta high density lipoprotein ( HDL ) . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
ABCA 1 dependent but apoA 1 independent cholesterol efflux mediated by fatty acid bile acid conjugates ( FABACs ) . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
Brain capillary endothelial cells , representing a physiological barrier to the central nervous system , express apolipoprotein A 1 ( apoA 1 , the major high density lipoprotein ( HDL ) associated apolipoprotein ) , ATP binding cassette transporter A 1 ( ABCA 1 ) , and scavenger receptor , class B , type 1 ( SR BI ) , proteins that promote cellular cholesterol mobilization . ^^^ Activation of LXR ( 24 ( S ) OH cholesterol , TO 901317 ) , PPARalpha ( bezafibrate , fenofibrate ) , and PPARgamma ( troglitazone , pioglitazone ) modulated expression of apoA 1 , ABCA 1 , and SR BI on mRNA and / or protein levels without compromising transendothelial electrical resistance or tight junction protein expression . ^^^ Along with the induction of cell surface located ABCA 1 , several agonists enhanced cholesterol mobilization in the presence of exogenous apoA 1 , while efflux of 24 ( S ) OH cholesterol ( the major brain cholesterol metabolite ) in the presence of exogenous HDL remained unaffected . ^^^ Summarizing , in cerebrovascular endothelial cells apoA 1 , ABCA 1 , and SR BI represent drug targets for LXR and PPAR agonists to interfere with cholesterol homeostasis at the periphery of the central nervous system . . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
Unlike previous results with hepatocytes and macrophages , neither apoA 1 nor upregulation of ABCA 1 stimulated apoE recycling . ^^^ Our data suggest that apoE recycling in CHO cells is linked to cellular cholesterol removal via the ERC and phospholipid containing acceptors in a pathway alternative to the ABCA 1 apoA 1 axis . . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
The ATP binding cassette , subfamily A , member 1 ( ABCA 1 ) mediates the rate controlling step in HDL particle formation , the assembly of free cholesterol and phospholipids with apoA 1 . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
The four major targets for an anti atherogenic strategy in HDL metabolism include stimulation of apoA 1 synthesis and secretion , the stimulation of ABCA 1 expression , the inhibition of cholesterol ester transfer protein , and the up regulation of scavenger receptor BI . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
Upregulation of cellular ABCA 1 protein by liver 10 receptor / retinoid 10 receptor agonists resulted in an increase of cellular lipid release by apoA 1 and SAA . ^^^ SAA reacted with the HEK 293 derived clones that stably express human ABCA 1 ( 293 / 2c ) or ABCA 7 ( 293 / 6c ) to generate cholesterol containing HDL in a similar manner to apoA 1 . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
In Tangier disease , the loss of the function of ABCA 1 , leads to an impaired formation of nascent high density lipoprotein particles by preventing the release of cellular phospholipids and cholesterol to the acceptor apolipoprotein A 1 . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
These include particles generated during lipidation of apoAI by ABCA 1 , suggesting that the two transporters cooperate in cholesterol export . ^^^ ABCA 1 dependent cholesterol export involves an initial interaction of apolipoprotein AI with lipid raft membrane domains , although ABCA 1 and most exported cholesterol are not raft associated . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
RECENT FINDINGS : Several novel mechanisms governing ABCA1 / apoA 1 interactions have recently been identified : apolipoprotein A 1 activates ABCA 1 phosphorylation through the cAMP / protein kinase A dependent pathway ; the majority of ABCA 1 exists as a tetramer in human living cell , supporting the concept that the homotetrameric ABCA 1 complex constitutes the minimum functional unit for the formation of nascent HDL particles ; apolipoprotein A 1 has been shown to have a recycling retroendocytic pathway with uptake and resecretion of the lipidated nascent HDL particles by the cell , most likely through the ABCA 1 transporter pathway ; there is evidence that the speciation of nascent HDL into pre beta and alpha HDL is linked to specific cell lines , and occurs by both ABCA 1 dependent and independent pathways . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
After cAMP treatment , which upregulated the expression of ABCA 1 , cholesterol efflux from PLTP KO foam cells to apoA 1 increased markedly and reached a level similar to that observed in cAMP treated WT foam cells , restoring the decreased cholesterol efflux associated with PLTP deficiency . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
Cyclosporin A ( CsA ) , an indirect inhibitor of protein phosphatase 2B ( PP2B ) and a potential inhibitor of ABC transporter A 1 ( ABCA 1 ) , suppressed all of these apoA 1 induced cellular events . ^^^ CsA thus interferes with cellular cholesterol homeostasis independently of PP2B inhibition , perhaps by direct inhibition of ABCA 1 reactivity to exogenous apoA 1 , although PP2B may be involved in the lipid release step . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
The ATP binding cassette transporter A 1 ( ABCA 1 ) regulates cell membrane phospholipid and cholesterol homeostasis and their release to lipid poor apolipoprotein AI to generate prebeta HDL precursor particles . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
Using localization of ABCA 1 , its ability to induce cell surface binding of apolipoprotein A 1 , and its ability to elicit efflux of cholesterol and phospholipids to apolipoprotein A 1 we determined that the phenotypes of patients correlate with the severity and nature of defects in ABCA 1 function . . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
Efflux experiments using the extracellular FC acceptors ( & bgr ; ) cyclodextrin or apolipoprotein A 1 demonstrated that TGD associated FC was releasable from TGD . ^^^
Interacting proteins: O95477 and P02647 Pubmed SVM Score :0.0
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