Protein Kinase C-δ Is Involved in Induction of NOX1 Gene Expression by Aldosterone in Rat Vascular Smooth Muscle Cells

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Haiyan Wei^1#, Xuhua Mi^2#, Ling Ji², Lichuan Yang², Qingjie Xia², Yuquan Wei³, Isamu Miyamori⁴, and ChunYuan Fan^2*

¹State Key Laboratory of Biotherapy, West China Hospital and School of Life Science, Sichuan University, Chengdu, China

²Department of Nephrology, State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, 1# Keyuan Road 4, Gaopeng Street, High Technological Development Zone, Chengdu 610041, China; fax: 86(28)8516-4005; E-mail: fanchunyuan2009@yahoo.cn; fanchunyuan38@yahoo.com.cn

³State Key Laboratory of Biotherapy, West China Hospital, Chengdu, China

⁴Third Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, Japan

^# These authors contributed equally to this work.

^* To whom correspondence should be addressed.

Received June 1, 2009; Revision received August 7, 2009

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In this study, we focused on the relationship between aldosterone and NOX1 expression in vascular smooth muscle cells (VSMCs). For the first time, with the use of specific inhibitors of protein kinase C (PKC), we report that PKCδ mediates upregulation of NOX1 induced by 10 nM aldosterone in cultured VSMCs. Participation of PKC in the mediation of NOX1 regulation was further confirmed by the effect of diacylglycerol, a PKC agonist, on the NOX1 RNA in A7r5 cells with Northern blot analysis. To establish cause and effect, we next silenced the PKCδ gene partly by RNA interference and found knockdown of PKCδ gene attenuated aldosterone-induced NOX1 expression, generation of superoxide, as well as protein synthesis in VSMCs. Taken together, these data indicated PKCδ might mediate aldosterone-dependent NOX1 upregulation in VSMCs. In addition, we showed that the cascade from aldosterone to PKCδ activation had the participation of the mineralocorticoid receptor.

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KEY WORDS: aldosterone, NOX1, PKCδ

DOI: 10.1134/S0006297910030065

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