cAMP induces ABCA1 phosphorylation activity and promotes cholesterol efflux from fibroblasts

Haidar, Bassam; Denis, Maxime; Krimbou, Larbi; Marcil, Michel; Genest, Jacques

doi:10.1194/jlr.m200235-jlr200

Cited by 97 publications

(108 citation statements)

References 33 publications

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“…We therefore investigated phosphorylation of ABCA1 by apoA-I. ABCA1 was phosphorylated with PKA activation by dibutyryl cAMP in both WI-38 and HEK293 cells expressing ABCA1-GFP, consistent with previous work by others (27,28) (Fig. 7, A and B).…”

Section: Fig 3 Pkc Regulates Apoa-i-induced Stabilization Of Abca1supporting

confidence: 58%

“…The phosphorylation and regulation of the activity of multidrug resistance P-glycoprotein by PKC and PKA have also been reported (49, 50). Furthermore, apoA-I-mediated cholesterol release and ABCA1 phosphorylation are both enhanced by activation of PKA by cAMP analogue (27,28). The same report (27) shows that mutation of its phosphorylation site (Ser-2054) results in impairment of the apoA-I-mediated lipid release, but PKA-dependent ABCA1 phosphorylation does not seem to be involved in its stability.…”

Section: Fig 3 Pkc Regulates Apoa-i-induced Stabilization Of Abca1mentioning

confidence: 60%

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Apolipoprotein A-I Activates Protein Kinase Cα Signaling to Phosphorylate and Stabilize ATP Binding Cassette Transporter A1 for the High Density Lipoprotein Assembly

Yamauchi

Hayashi

Abe-Dohmae

et al. 2003

Journal of Biological Chemistry

129

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Section: Fig 3 Pkc Regulates Apoa-i-induced Stabilization Of Abca1supporting

confidence: 58%

Section: Fig 3 Pkc Regulates Apoa-i-induced Stabilization Of Abca1mentioning

confidence: 60%

Apolipoprotein A-I Activates Protein Kinase Cα Signaling to Phosphorylate and Stabilize ATP Binding Cassette Transporter A1 for the High Density Lipoprotein Assembly

Yamauchi

Hayashi

Abe-Dohmae

et al. 2003

Journal of Biological Chemistry

129

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“…The constitutive phosphorylation of Ser-1042 and Ser-2054 by PKA in human ABCA1 increases ABCA1-mediated phospholipid efflux. However, PKA activity has no effect on ABCA1 expression (48,49). ApoAI and synthetic amphiphilic helical peptides increase ABCA1 protein stability by activating PKA (50,51).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of ERK1/2 and Activation of Liver X Receptor Synergistically Induce Macrophage ABCA1 Expression and Cholesterol Efflux

Zhou

Yin

Guo

et al. 2010

Journal of Biological Chemistry

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ATP-binding cassette transporter A1 (ABCA1), a molecule mediating free cholesterol efflux from peripheral tissues to apoAI and high density lipoprotein (HDL), inhibits the formation of lipid-laden macrophage/foam cells and the development of atherosclerosis. ERK1/2 are important signaling molecules regulating cellular growth and differentiation. The ERK1/2 signaling pathway is implicated in cardiac development and hypertrophy. However, the role of ERK1/2 in the development of atherosclerosis, particularly in macrophage cholesterol homeostasis, is unknown. In this study, we investigated the effects of ERK1/2 activity on macrophage ABCA1 expression and cholesterol efflux. Compared with a minor effect by inhibition of other kinases, inhibition of ERK1/2 significantly increased macrophage cholesterol efflux to apoAI and HDL. In contrast, activation of ERK1/2 reduced macrophage cholesterol efflux and ABCA1 expression. The increased cholesterol efflux by ERK1/2 inhibitors was associated with the increased ABCA1 levels and the binding of apoAI to cells. The increased ABCA1 by ERK1/2 inhibitors was due to increased ABCA1 mRNA and protein stability. The induction of ABCA1 expression and cholesterol efflux by ERK1/2 inhibitors was concentration-dependent. The mechanism study indicated that activation of liver X receptor (LXR) had little effect on ERK1/2 expression and activation. ERK1/2 inhibitors had no effect on macrophage LXR␣/␤ expression, whereas they did not influence the activation or the inhibition of the ABCA1 promoter by LXR or sterol regulatory element-binding protein (SREBP). However, inhibition of ERK1/2 and activation of LXR synergistically induced macrophage cholesterol efflux and ABCA1 expression. Our data suggest that ERK1/2 activity can play an important role in macrophage cholesterol trafficking.Development of atherosclerotic lesions in coronary arteries is an underlying cause of coronary heart disease. Lipid-laden macrophage/foam cells are a prominent part of atherosclerotic lesions (1). Cellular cholesterol content in macrophages is determined by uptake and efflux of cholesterol (2). The type A scavenger receptor and type B scavenger receptor (CD36) mediate the binding and internalization of modified low density lipoprotein (LDL), 3 thus, demonstrating pro-atherogenic properties (3, 4). In contrast, type BI scavenger receptor and ATPbinding cassette transporter A1 (ABCA1) can mediate cellular free cholesterol efflux to extracellular high density lipoprotein (HDL) or lipid-free apolipoprotein AI (apoAI) thereby inhibiting the development of atherosclerosis (5, 6). Compared with bi-directional cholesterol transport across cellular membranes that are mediated by type BI scavenger receptor (7, 8), ABCA1 stimulates free cholesterol efflux from macrophages and other peripheral cell types to apoAI and/or HDL by using the energy from ATP hydrolysis (9). The binding of free cholesterol and phospholipids to apoAI also leads to the generation of nascent HDL (10). ABCA1 can also mediate cholesterol efflux to exog...

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“…Furthermore, recent studies from our laboratory and others have shown that ABCA1 phosphorylation by cAMP/PKA-dependent pathway plays an important role in the apoA-I lipidation reaction (20,34,35), suggesting that lipidation of apoA-I by ABCA1 is an active process. We confirmed and extended this observation by showing that 125 I-apoA-I dissociation from ABCA1 was almost completely inhibited at either 4 or 15°C (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…Cells were lysed at 4°C with IP buffer containing 20 mM Tris (pH 7.5), 0.5 mM EDTA, 0.5 mM EGTA, 1% Triton X-100 (Invitrogen), and the suspension was allowed to stand for 30 min at 4°C in presence of a protease inhibitor mixture (Roche Diagnostics). ApoA-I/ABCA1 complex was immunoprecipitated with an affinity-purified polyclonal anti-ABCA1 antibody (Novus Biologicals) as previously described (20). After SDS-gel electrophoresis either apoA-I or ABCA1 were detected by immunopurified polyclonal anti-apoA-I antibody (Biodesign) or affinity-purified human anti-ABCA1 antibody (Novus).…”

mentioning

confidence: 99%

Molecular and Cellular Physiology of Apolipoprotein A-I Lipidation by the ATP-binding Cassette Transporter A1 (ABCA1)

Denis

Haidar

Marcil

et al. 2004

Journal of Biological Chemistry

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A time course analysis of apoA-I-containing particles released during the dissociation period showed nascent apoA-I-phospholipid complexes that exhibited ␣-electrophoretic mobility with a particle size ranging from 9 to 20 nm (designated ␣-LpA-I-like particles), whereas lipid-free apoA-I incubated with ABCA1 mutant (Q597R) cells was unable to form such particles. These results demonstrate that: 1) the physical interaction of apoA-I with ABCA1 does not depend on membrane phosphatidylcholine or sphingomyelin; 2) the association of apoA-I with lipids reduces its ability to interact with ABCA1; and 3) the lipid translocase activity of ABCA1 generates ␣-LpA-I-like particles. This process plays in vivo a key role in HDL biogenesis.

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cAMP induces ABCA1 phosphorylation activity and promotes cholesterol efflux from fibroblasts

Cited by 97 publications

References 33 publications

Apolipoprotein A-I Activates Protein Kinase Cα Signaling to Phosphorylate and Stabilize ATP Binding Cassette Transporter A1 for the High Density Lipoprotein Assembly

Apolipoprotein A-I Activates Protein Kinase Cα Signaling to Phosphorylate and Stabilize ATP Binding Cassette Transporter A1 for the High Density Lipoprotein Assembly

Inhibition of ERK1/2 and Activation of Liver X Receptor Synergistically Induce Macrophage ABCA1 Expression and Cholesterol Efflux

Molecular and Cellular Physiology of Apolipoprotein A-I Lipidation by the ATP-binding Cassette Transporter A1 (ABCA1)

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