12/13 mediates α1-adrenergic receptor-induced cardiac hypertrophy

Yoshiko Maruyama, Motohiro Nishida, Yoshiyuki Sugimoto, Shihori Tanabe, Justin H. Turner, Tohru Kozasa, Teiji Wada, Taku Nagao, Hitoshi Kurose

Research output: Contribution to journalArticle

88 Citations (Scopus)

Abstract

In neonatal cardiomyocytes, activation of the Gq-coupled α1-adrenergic receptor (α1AR) induces hypertrophy by activating mitogen-activated protein kinases, including c-Jun NH2-terminal kinase (JNK). Here, we show that JNK activation is essential for α1AR-induced hypertrophy, in that α1AR-induced hypertrophic responses, such as reorganization of the actin cytoskeleton and increased protein synthesis, could be blocked by expressing the JNK-binding domain of JNK-interacting protein-1, a specific inhibitor of JNK. We also identified the classes and subunits of G proteins that mediate α1AR-induced JNK activation and hypertrophic responses by generating several recombinant adenoviruses that express polypeptides capable of inhibiting the function of specific G-protein subunits. α1AR-induced JNK activation was inhibited by the expression of carboxyl terminal regions of Gαq, Gα12, and Gα13. JNK activation was also inhibited by the Gαq/11- or Gα12/13-specific regulator of G-protein signaling (RGS) domains and by C3 toxin but was not affected by treatment with pertussis toxin or by expression of the carboxyl terminal region of G protein-coupled receptor kinase 2, a polypeptide that sequesters Gβγ. α1AR-induced hypertrophic responses were inhibited by Gαq/11- and Gα12/13-specific RGS domains, C3 toxin, and the carboxyl terminal region of G protein-coupled receptor kinase 2 but not by pertussis toxin. Activation of Rho was inhibited by carboxyl terminal regions of Gα12 and Gα13 but not by Gαq. Our findings suggest that α1AR-induced hypertrophic responses are mediated in part by a Gα12/13-Rho-JNK pathway, in part by a Gq/11-JNK pathway that is Rho independent, and in part by a Gβγ pathway that is JNK independent.

Original languageEnglish
Pages (from-to)961-969
Number of pages9
JournalCirculation research
Volume91
Issue number10
DOIs
Publication statusPublished - Nov 15 2002

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cardiology and Cardiovascular Medicine

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