Angiotensin II activates p44/42 MAP kinase partly through PKCε in H295R cells

MOLECULAR AND CELLULAR ENDOCRINOLOGY

卷:265

Article; Proceedings Paper

LeHoux, Jean-Guy ; Lefebvre, Andree

关键词: CYP11B2 gene;    P450 aldosterone synthase;    PKC epsilon;    ERK;    p44/42 MAPK;    angiotensin II;   

DOI  :  10.1016/j.mce.2006.12.027

来源: Elsevier

【 摘 要 】

Using pharmaceutical and overexpression approaches we have previously reported that in H295R cells, (a) angiotensin II (AII) activates PKC epsilon, PKC alpha and p44/42 MAPK pathway, (b) PKC epsilon, PKC alpha and p44/42 MAPK overexpression inhibits All-induced CYP11B2 gene transcription and (c) overexpression of PKC epsilon inhibits CYP11B2 gene transcription through p44/42 MAPK activation [LeHoux, J.G., Dupuis, G., Lefebvre, A., 2001. Control of CYP11B2 gene expression through differential regulation of its promoter by atypical and conventional protein kinase C isoforms. J. Biol. Chem. 276 (11), 8021-8028; LeHoux, J.G., Lefebvre, A., 2006. Novel protein kinase C-epsilon inhibits human CYP11B2 gene expression through ERK1/2 signalling pathway and JunB. J. Mol. Endocrinol. 36 (1), 51-64]. The aim of the present work was to evaluate the physiological role of endogenous PKC epsilon and PKC alpha isoforms in the activation of p44/42 MAPK by AII. A 50% reduction of PKC epsilon protein by siRNA-PKC epsilon resulted in 35% inhibition of AII-induced p44/42 MAPK activation. Knockdown of PKC epsilon stimulated AII-induced CYP11B2 transcription indicating that the PKC epsilon is not involved in the activation of CYP11B2 gene expression by All. Furthermore, knockdown of PKC alpha enhanced AII-stimulated CYP11B2 transcription without altering p44/42 MAPK indicating that inhibition of All-stimulated CYP11B2 gene by PKC epsilon does not involve the p44/42 MAPK signalling pathway. These results thus establish that physiologically, PKC epsilon and PKC alpha act through different signalling pathways to inhibit All-stimulated CYP11B2 gene expression. (c) 2007 Published by Elsevier Ireland Ltd.

【 授权许可】

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