Protein kinase C-delta is involved in induction of NOX1 gene expression by aldosterone in rat vascular smooth muscle cells.
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 PKCdelta 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 PKCdelta gene partly by RNA interference and found knockdown of PKCdelta gene attenuated aldosterone-induced NOX1 expression, generation of superoxide, as well as protein synthesis in VSMCs. Taken together, these data indicated PKCdelta might mediate aldosterone-dependent NOX1 upregulation in VSMCs. In addition, we showed that the cascade from aldosterone to PKCdelta activation had the participation of the mineralocorticoid receptor.
Wei
Haiyan
H
State Key Laboratory of Biotherapy, West China Hospital and School of Life Science, Sichuan University, Chengdu, China.
Mi
Xuhua
X
Ji
Ling
L
Yang
Lichuan
L
Xia
Qingjie
Q
Wei
Yuquan
Y
Miyamori
Isamu
I
Fan
Chunyuan
C
D000450:Aldosterone / Q000494:pharmacology*; D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology*; D020868:Gene Silencing; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects*; D009247:NADH, NADPH Oxidoreductases / Q000235:genetics*; D000074624:NADPH Oxidase 1; D051745:Protein Kinase C-delta / Q000235:genetics / Q000502:physiology*; D051381:Rats
D017931:DNA Primers; D000450:Aldosterone; D009247:NADH, NADPH Oxidoreductases; D000074624:NADPH Oxidase 1; C000614712:NOX1 protein, rat; D051745:Protein Kinase C-delta