Protein kinase C epsilon-dependent extracellular signal-regulated kinase 5 phosphorylation and nuclear translocation involved in cardiomyocyte hypertrophy with angiotensin II stimulation.
Angiotensin II (Ang II) plays a critical role in hypertrophy of cardiomyocytes; however, the molecular mechanism, especially the signaling cascades, in cardiomyocytes remains unclear. In the present study, we examined the mechanism of Ang II in hypertrophy of cardiomyocytes. Ang II rapidly stimulated phosphorylation of protein kinase C epsilon (PKCepsilon) in a time- and dose-dependent manner via Ang II receptor-1 (AT(1)). Furthermore, Ang II-induced extracellular signal-regulated kinase 5 (ERK5) phosphorylation and translocation was mediated through a signal pathway that involves AT(1) and PKCepsilon, which resulted in transcriptional activation of myocyte enhancer factor-2C (MEF2C) and hypertrophy. Consequently, inhibiting PKCepsilon or ERK5 by small interfering RNA (siRNA) significantly attenuated Ang II-induced MEF2C activation and hypertrophy of rat cardiomyocytes. These data provide evidence that PKCepsilon-dependent ERK5 phosphorylation and nucleocytoplasmic traffic mediates Ang II-induced MEF2C activation and cardiomyocyte hypertrophy. PKCepsilon and ERK5 may be potential targets in the treatment of pathological vascular hypertrophy associated with the enhanced renin-angiotensin system.
Zhao
Zhuo
Z
The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Shandong University Qilu Hospital, Shandong, PR China.
Wang
Wei
W
Geng
Jing
J
Wang
Liqi
L
Su
Guohai
G
Zhang
Yun
Y
Ge
Zhiming
Z
Kang
Weiqiang
W
D021581:Active Transport, Cell Nucleus; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D049108:Cell Enlargement; D006984:Hypertrophy / Q000378:metabolism*; D064326:MEF2 Transcription Factors; D048054:Mitogen-Activated Protein Kinase 7 / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000473:pathology*; D018006:Myogenic Regulatory Factors / Q000378:metabolism; D010766:Phosphorylation; D051744:Protein Kinase C-epsilon / Q000037:antagonists & inhibitors / Q000502:physiology*; D051381:Rats
D064326:MEF2 Transcription Factors; C578042:MEF2C protein, rat; D018006:Myogenic Regulatory Factors; D000804:Angiotensin II; D051744:Protein Kinase C-epsilon; D048054:Mitogen-Activated Protein Kinase 7