Activation of p70 S6 protein kinase is necessary for angiotensin II-induced hypertrophy in neonatal rat cardiac myocytes.
Although many lines of evidence have suggested that angiotensin II (Ang II) plays an important role in development of cardiac hypertrophy, the mechanism by which Ang II increases protein synthesis in cardiac myocytes remains unclear. It has been reported that the phosphorylation of S6 protein in 40 S ribosome is correlated to the efficiency of protein synthesis. In the present study, we have examined whether Ang II activates p70 S6 kinase (p70S6K), which has been reported to phosphorylate S6 protein. Ang II activated p70S6K through AT1 receptor. An immunosuppressant agent, rapamycin, inhibited Ang II-induced p70S6K activation but not the activation of MAP kinases or the induction of c-fos gene expression. Rapamycin also abolished Ang II-induced increase in protein synthesis. These results suggest that Ang II induces cardiac hypertrophy by activating p70S6K.
Takano
H
H
Department of Medicine III, University of Tokyo School of Medicine, Japan.
Komuro
I
I
Zou
Y
Y
Kudoh
S
S
Yamazaki
T
T
Yazaki
Y
Y
D000803:Angiotensin I / Q000378:metabolism; D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D006332:Cardiomegaly / Q000378:metabolism; D002478:Cells, Cultured; D004789:Enzyme Activation; D015870:Gene Expression; D016762:Genes, fos; D007166:Immunosuppressive Agents / Q000494:pharmacology; D009206:Myocardium / Q000166:cytology / Q000201:enzymology*; D010766:Phosphorylation; D011090:Polyenes / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011945:Receptors, Angiotensin / Q000378:metabolism; D019893:Ribosomal Protein S6 Kinases; D020123:Sirolimus
D057911:Angiotensin Receptor Antagonists; D007166:Immunosuppressive Agents; D011090:Polyenes; D011945:Receptors, Angiotensin; D000804:Angiotensin II; D000803:Angiotensin I; D017346:Protein Serine-Threonine Kinases; D019893:Ribosomal Protein S6 Kinases; D020123:Sirolimus