Dihydrotestosterone regulating apolipoprotein M expression mediates via protein kinase C in HepG2 cells

Lipids in Health and Disease

Research

Cao Bing¹  Ye Yi-zhou²  Ji Yong³  Wei Liu-yan³  Rui Jun³  Jing Zhao-hui³  Jiao Guo qing³  Li Ming-qiu³  Wang Ru-xing³  Zou Jian³  Wang Wei⁴ 

[1] Department of Cardiothoracic Surgery, Affiliated Taixing People’s Hospital, Yangzhou Medical University, 225400, Taixing, People's Republic of China;Department of Cardiovascular Surgery, Affiliated Shanghai 1st People’s Hospital, Shanghai Jiaotong University, 210008, Shanghai, People's Republic of China;Department of Cardiovascular Surgery, Affiliated Wuxi People’s Hospital, Nanjing Medical University, Qingyang Road 299, 214023, Wuxi City, Jiangsu Province, China;Department of Cardiovascular Surgery, National Center for Cardiovascular Disease, 200000, Beijing, People's Republic of China;

关键词: Androgen;    DHT;    ApoM;    PKC;   

DOI  :  10.1186/1476-511X-11-168

 received in 2012-09-22, accepted in 2012-11-20,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundAdministration of androgens decreases plasma concentrations of high-density lipid cholesterol (HDL-C). However, the mechanisms by which androgens mediate lipid metabolism remain unknown. This present study used HepG2 cell cultures and ovariectomized C57BL/6 J mice to determine whether apolipoprotein M (ApoM), a constituent of HDL, was affected by dihydrotestosterone (DHT).MethodsHepG2 cells were cultured in the presence of either DHT, agonist of protein kinase C (PKC), phorbol-12-myristate-13-acetate (PMA), blocker of androgen receptor flutamide together with different concentrations of DHT, or DHT together with staurosporine at different concentrations for 24 hrs. Ovariectomized C57BL/6 J mice were treated with DHT or vehicle for 7d or 14d and the levels of plasma ApoM and livers ApoM mRNA were measured. The mRNA levels of ApoM, ApoAI were determined by real-time RT-PCR. ApoM and ApoAI were determined by western blotting analysis.ResultsAddition of DHT to cell culture medium selectively down-regulated ApoM mRNA expression and ApoM secretion in a dose-dependent manner. At 10 nM DHT, the ApoM mRNA levels were about 20% lower than in untreated cells and about 40% lower at 1000 nM DHT than in the control cells. The secretion of ApoM into the medium was reduced to a similar extent. The inhibitory effect of DHT on ApoM secretion was not blocked by the classical androgen receptor blocker flutamide but by an antagonist of PKC, Staurosporine. Agonist of PKC, PMA, also reduced ApoM. At 0.5 μM PMA, the ApoM mRNA levels and the secretion of ApoM into the medium were about 30% lower than in the control cells. The mRNA expression levels and secretion of another HDL-associated apolipoprotein AI (ApoAI) were not affected by DHT. The levels of plasma ApoM and liver ApoM mRNA of DHT-treated C57BL/6 J mice were lower than those of vehicle-treated mice.ConclusionsDHT directly and selectively down-regulated the level of ApoM mRNA and the secretion of ApoM by protein kinase C but independently of the classical androgen receptor.

【 授权许可】

Unknown   
© Yi-zhou et al.; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.