A requirement for the rac1 GTPase in the signal transduction pathway leading to cardiac myocyte hypertrophy

John B. Pracyk, Koichi Tanaka, Donald D. Hegland, Kyung Soo Kim, Rachna Sethi, Ilsa I. Rovira, David R. Blazina, Larisse Lee, Joseph T. Bruder, Imre Kovesdi, Pascal J. Goldshmidt-Clermont, Kaikobad Irani, Toren Finkel

Research output: Contribution to journalArticle

Abstract

We have used adenoviral-mediated gene transfer of a constitutively active (V12rac1) and dominant negative (N17rac1) isoform of rac1 to assess the role of this small GTPase in cardiac myocyte hypertrophy. Expression of V12rac1 in neonatal cardiac myocytes results in sarcomeric reorganization and an increase in cell size that is indistinguishable from ligand-stimulated hypertrophy. In addition, V12rac1 expression leads to an increase in atrial natriuretic peptide secretion. In contrast, expression of N17rac1, but not a truncated form of Raf-1, attenuated the morphological hypertrophy associated with phenylephrine stimulation. Consistent with the observed effects on morphology, expression of V12rac1 resulted in an increase in new protein synthesis, while N17rac1 expression inhibited phenylephrine-induced leucine incorporation. These results suggest rac1 is an essential element of the signaling pathway leading to cardiac myocyte hypertrophy.

Original languageEnglish (US)
Pages (from-to)929-937
Number of pages9
JournalJournal of Clinical Investigation
Volume102
Issue number5
StatePublished - Sep 1 1998
Externally publishedYes

Keywords

  • GTPase
  • Hypertrophy
  • Myocyte
  • rac1
  • Signal transduction

ASJC Scopus subject areas

  • Medicine(all)

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  • Cite this

    Pracyk, J. B., Tanaka, K., Hegland, D. D., Kim, K. S., Sethi, R., Rovira, I. I., Blazina, D. R., Lee, L., Bruder, J. T., Kovesdi, I., Goldshmidt-Clermont, P. J., Irani, K., & Finkel, T. (1998). A requirement for the rac1 GTPase in the signal transduction pathway leading to cardiac myocyte hypertrophy. Journal of Clinical Investigation, 102(5), 929-937.