Rho plays an important role in angiotensin II-induced hypertrophic responses in cardiac myocytes.
Angiotensin II (Ang II) evokes a variety of hypertrophic responses such as activation of protein kinases, reprogramming of gene expressions and an increase in protein synthesis in cardiac myocytes. In this study, we examined the role of Rho family small GTP binding proteins (G proteins) in Ang II-induced cardiac hypertrophy. Ang II strongly activated extracellular signal-regulated protein kinases (ERKs) in cardiac myocytes of neonatal rats. Although Ang II-induced activation of ERKs was completely suppressed by an Ang II type 1 receptor antagonist, CV-11974, this activation was not inhibited by the pretreatment with C3 exoenzyme, which abrogates Rho functions. Overexpression of Rho GDP dissociation inhibitor (Rho-GDI), dominant negative mutants of Rac1 (D.N.Rac1), or D.N.Cdc42 had no effects on Ang II-induced activation of transfected ERK2. The promoter activity of skeletal alpha-actin and c-fos genes was increased by Ang II, and the increase was partly inhibited by overexpression of Rho-GDI and the pretreatment with C3 exoenzyme. Ang II increased phenylalanine incorporation into cardiac myocytes by approximately 1.4 fold as compared with control, and this increase was also significantly suppressed by the pretreatment with C3 exoenzyme. These results suggest that the Rho family small G proteins play important roles in Ang II-induced hypertrophic responses in cardiac myocytes.
Aikawa
R
R
Department of Cardiovascular Medicine, University of Tokyo Graduate School of Medicine, Japan.
Komuro
I
I
Nagai
R
R
Yazaki
Y
Y
D000199:Actins / Q000235:genetics; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D006332:Cardiomegaly; D002478:Cells, Cultured; D004789:Enzyme Activation; D005786:Gene Expression Regulation / Q000187:drug effects; D016762:Genes, fos; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009206:Myocardium / Q000166:cytology; D011401:Promoter Regions, Genetic; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000378:metabolism; D014162:Transfection; D020741:rho GTP-Binding Proteins / Q000378:metabolism*
D000199:Actins; D011994:Recombinant Proteins; D000804:Angiotensin II; D019950:Mitogen-Activated Protein Kinase 1; D020928:Mitogen-Activated Protein Kinases; D020741:rho GTP-Binding Proteins