The effects of the selective ROCK inhibitor, Y27632, on ET-1-induced hypertrophic response in neonatal rat cardiac myocytes - Possible involvement of Rho/ROCK pathway in cardiac muscle cell hypertrophy

Koichiro Kuwahara, Yoshihiko Saito, Osamu Nakagawa, Ichiro Kishimoto, Masaki Harada, Emiko Ogawa, Yoshihiro Miyamoto, Ichiro Hamanaka, Noboru Kajiyama, Nobuki Takahashi, Takehiko Izumi, Rika Kawakami, Naohisa Tamura, Yoshihiro Ogawa, Kazuwa Nakao

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Abstract

A small GTPase, Rho, participates in agonist-induced cytoskeletal organization and gene expression in many cell types including cardiac myocytes. However, little is known about the functions of Rho's downstream targets in cardiac myocytes. We examined the role of ROCK, a downstream target of Rho, in ET-1-induced hypertrophic response. Y27632, a selective ROCK inhibitor, inhibited ET-1-induced increases in natriuretic peptide production, cell size, protein synthesis, and myofibrillar organization. In addition, a dominant-negative mutant of p160ROCK suppressed ET-1-induced transcription of the BNP gene. These findings suggest that the Rho/ROCK pathway is an important component of ET-1-induced hypertrophic signals in cardiac myocytes. Copyright (C) 1999 Federation of European Biochemical Societies.

Original languageEnglish
Pages (from-to)314-318
Number of pages5
JournalFEBS Letters
Volume452
Issue number3
DOIs
Publication statusPublished - Jun 11 1999
Externally publishedYes

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All Science Journal Classification (ASJC) codes

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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