Angiotensin II activates p44/42 MAP kinase partly through PKCepsilon in H295R cells.
Using pharmaceutical and overexpression approaches we have previously reported that in H295R cells, (a) angiotensin II (AII) activates PKCepsilon, PKCalpha and p44/42 MAPK pathway, (b) PKCepsilon, PKCalpha and p44/42 MAPK overexpression inhibits AII-induced CYP11B2 gene transcription and (c) overexpression of PKCepsilon 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 PKCepsilon and PKCalpha isoforms in the activation of p44/42 MAPK by AII. A 50% reduction of PKCepsilon protein by siRNA-PKCepsilon resulted in 35% inhibition of AII-induced p44/42 MAPK activation. Knockdown of PKCepsilon stimulated AII-induced CYP11B2 transcription indicating that the PKCepsilon is not involved in the activation of CYP11B2 gene expression by AII. Furthermore, knockdown of PKCalpha enhanced AII-stimulated CYP11B2 transcription without altering p44/42 MAPK indicating that inhibition of AII-stimulated CYP11B2 gene by PKCalpha does not involve the p44/42 MAPK signalling pathway. These results thus establish that physiologically, PKCepsilon and PKCalpha act through different signalling pathways to inhibit AII-stimulated CYP11B2 gene expression.
Lehoux
Jean-Guy
JG
Department of Biochemistry, Faculty of Medicine and Health Sciences, University of Sherbrooke, Sherbrooke, Quebec, Canada J1H 5N4. jean-guy.lehoux@usherbrooke.ca
Lefebvre
Andrée
A
D000804:Angiotensin II / Q000378:metabolism*; D045744:Cell Line, Tumor; D019405:Cytochrome P-450 CYP11B2 / Q000235:genetics; D006801:Humans; D020935:MAP Kinase Signaling System; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D051571:Protein Kinase C-alpha / Q000235:genetics / Q000378:metabolism; D051744:Protein Kinase C-epsilon / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering
D034741:RNA, Small Interfering; D000804:Angiotensin II; D019405:Cytochrome P-450 CYP11B2; D051571:Protein Kinase C-alpha; D051744:Protein Kinase C-epsilon; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3