title: Apelin-13 increases expression of ATP-binding cassette transporter A1 via activating protein kinase C α signaling in THP-1 macrophage-derived foam cells.
abstract: Apelin has an antiatherogenic function through activating protein kinase C (PKC) to initiate a series of cellular signaling pathways. PKC phosphorylates and stabilizes ATP-binding cassette transporter A1 (ABCA1) through inhibiting its degradation mediated by calpain. Thus, in the present study, we investigated whether apelin-13 affects expression of ABCA1 through PKC signaling. The results showed that apelin-13 dramatically increased cholesterol efflux from THP-1 macrophage-derived foam cells and reduced cellular cholesterol levels. ABCA1 protein but not mRNA levels were dramatically increased by apelin-13, and calpain-induced degradation of ABCA1 and calpain activity were suppressed with treatment of apelin-13. However, the effects of apelin-13 on ABCA1 protein expression, cellular cholesterol efflux and calpain activity were abolished by depletion of PKCα, suggesting the potential important role of PKCα. In addition, apelin-13 was shown to phosphorylate serine residues in ABCA1 through the PKCα pathway. Thus, apelin-13 appears to activate PKCα, phosphorylate ABCA1 and inhibit calpain-mediated proteolysis, thereby promoting cholesterol efflux and reducing foam cell formation. Our study herein described a possible mechanism for understanding the antiatherogenic effects of apelin on attenuating the progression of atherosclerosis.
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Life Science Research Center, University of South China, Hengyang, Hunan 421001, China.
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Liu
authors.forename: Qian
authors.initials: Q
authors.lastname: Lu
authors.forename: Xin-Ping
authors.initials: XP
authors.lastname: Ouyang
authors.forename: Shi-Lin
authors.initials: SL
authors.lastname: Tang
authors.forename: Guo-Jun
authors.initials: GJ
authors.lastname: Zhao
authors.forename: Yun-Cheng
authors.initials: YC
authors.lastname: Lv
authors.forename: Ping-Ping
authors.initials: PP
authors.lastname: He
authors.forename: Hai-Jun
authors.initials: HJ
authors.lastname: Kuang
authors.forename: Yan-Yan
authors.initials: YY
authors.lastname: Tang
authors.forename: Yuchang
authors.initials: Y
authors.lastname: Fu
authors.forename: Da-Wei
authors.initials: DW
authors.lastname: Zhang
authors.forename: Chao-Ke
authors.initials: CK
authors.lastname: Tang
mesh_terms: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis*; D002154:Calpain / Q000037:antagonists & inhibitors / Q000378:metabolism; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism; D005487:Foam Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology*; D008264:Macrophages / Q000378:metabolism; D051571:Protein Kinase C-alpha / Q000378:metabolism*
chemical_list: C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D036341:Intercellular Signaling Peptides and Proteins; C495199:apelin-13 peptide; D002784:Cholesterol; D051571:Protein Kinase C-alpha; D002154:Calpain