Abstract：
:ATP-binding cassette transporter A1 (ABCA1) plays a crucial role in apoA-I lipidation, a key step in reverse cholesterol transport. cAMP induces apoA-I binding activity and promotes cellular cholesterol efflux. We investigated the role of the cAMP/protein kinase A (PKA) dependent pathway in the regulation of cellular cholesterol efflux. Treatment of normal fibroblasts with 8-bromo-cAMP (8-Br-cAMP) increased significantly apoA-I-mediated cholesterol efflux, with specificity for apoA-I, but not for cyclodextrin. Concomitantly, 8-Br-cAMP increased ABCA1 phosphorylation in a time-dependent manner. Maximum phosphorylation was reached in <10 min, representing a 260% increase compared to basal ABCA1 phosphorylation level. Forskolin, a known cAMP regulator, increased both cellular cholesterol efflux and ABCA1 phosphorylation. In contrast, H-89 PKA inhibitor reduced cellular cholesterol efflux by 70% in a dose-dependent manner and inhibited almost completely ABCA1 phosphorylation. To determine whether naturally occurring mutants of ABCA1 may affect its phosphorylation activity, fibroblasts from subjects with familial HDL deficiency (FHD, heterozygous ABCA1 defect) and Tangier disease (TD, homozygous/compound heterozygous ABCA1 defect) were treated with 8-Br-cAMP or forskolin. Cellular cholesterol efflux and ABCA1 phosphorylation were increased in FHD but not in TD cells. Taken together, these findings provide evidence for a link between the cAMP/PKA-dependent pathway, ABCA1 phosphorylation, and apoA-I mediated cellular cholesterol efflux.
journal_name
J Lipid Resjournal_title
Journal of lipid researchauthors
Haidar B,Denis M,Krimbou L,Marcil M,Genest J Jrdoi
10.1194/jlr.m200235-jlr200keywords:
subject
Has Abstractpub_date
2002-12-01 00:00:00pages
2087-94issue
12eissn
0022-2275issn
1539-7262journal_volume
43pub_type
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journal_title：Journal of lipid research
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journal_title：Journal of lipid research
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更新日期：1978-03-01 00:00:00
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journal_title：Journal of lipid research
pub_type： 临床试验,杂志文章
doi：10.1194/jlr.M200439-JLR200
更新日期：2003-04-01 00:00:00
abstract：:PAF-dependent transacetylase (TA) modifies the functions of platelet-activating factor (PAF), a potent inflammatory lipid, either by transferring the acetyl group from PAF to lysophospholipids (TAL activity), or to sphingosine (TAS activity) or by hydrolyzing PAF (acetylhydrolase activity). In stimulated endothelial c...
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doi：10.1194/jlr.M200292-JLR200
更新日期：2003-02-01 00:00:00
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journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1989-04-01 00:00:00
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journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1995-06-01 00:00:00
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journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M600297-JLR200
更新日期：2006-11-01 00:00:00
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journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M300091-JLR200
更新日期：2003-08-01 00:00:00
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pub_type： 杂志文章
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更新日期：2008-07-01 00:00:00
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journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1966-01-01 00:00:00
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journal_title：Journal of lipid research
pub_type： 杂志文章,评审
doi：
更新日期：1984-12-15 00:00:00
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journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1997-08-01 00:00:00
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journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1998-04-01 00:00:00
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journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1998-02-01 00:00:00
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journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1976-05-01 00:00:00
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journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1996-12-01 00:00:00
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pub_type： 杂志文章
doi：10.1194/jlr.M016048
更新日期：2011-12-01 00:00:00
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pub_type： 杂志文章
doi：10.1194/jlr.M081299
更新日期：2018-01-01 00:00:00
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journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1977-01-01 00:00:00
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doi：10.1194/jlr.TR120001137
更新日期：2020-10-26 00:00:00
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journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M400064-JLR200
更新日期：2004-07-01 00:00:00
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pub_type： 杂志文章
doi：10.1194/jlr.RA120000704
更新日期：2020-12-15 00:00:00
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journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1976-09-01 00:00:00
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journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1968-01-01 00:00:00
abstract：:Rat liver microsomes were incubated with the monofunctional aminoreagent fluorescamine. Although the probe easily penetrated the membranes, two pools of phosphatidylethanolamine (PE) could be detected. The first pool rapidly reacted with the probe and comprised 80% of the total PE. The second pool exhibited a very slo...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1986-07-01 00:00:00
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journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1982-05-01 00:00:00
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更新日期：2016-02-01 00:00:00
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更新日期：2003-10-01 00:00:00
