期刊
ATHEROSCLEROSIS
卷 226, 期 2, 页码 398-407出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.atherosclerosis.2012.12.002
关键词
Apelin; ABCA1; PKC alpha; Calpain; Atherosclerosis
资金
- National Natural Sciences Foundation of China [81070220, 81170278]
- Aid Program for Science and Technology Innovative Research Team in Higher Educational Institutions of Human Province, China [2008-244]
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 PKC alpha, suggesting the potential important role of PKC alpha. In addition, apelin-13 was shown to phosphorylate serine residues in ABCA1 through the PKC alpha pathway. Thus, apelin-13 appears to activate PKC alpha, 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. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
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