Myosin regulatory light chain phosphorylation attenuates cardiac hypertrophy

Jian Huang, John M. Shelton, James A. Richardson, Kristine E. Kamm, James T. Stull

Research output: Contribution to journalArticle

43 Scopus citations

Abstract

Hyperphosphorylation of myosin regulatory light chain (RLC) in cardiac muscle is proposed to cause compensatory hypertrophy. We therefore investigated potential mechanisms in genetically modified mice. Transgenic (TG) mice were generated to overexpress Ca2+/calmodulin-dependent myosin light chain kinase specifically in cardiomyocytes. Phosphorylation of sarcomeric cardiac RLC and cytoplasmic nonmuscle RLC increased markedly in hearts from TG mice compared with hearts from wild-type (WT) mice. Quantitative measures of RLC phosphorylation revealed no spatial gradients. No significant hypertrophy or structural abnormalities were observed up to 6 months of age in hearts of TG mice compared with WT animals. Hearts and cardiomyocytes from WT animals subjected to voluntary running exercise and isoproterenol treatment showed hypertrophic cardiac responses, but the responses for TG mice were attenuated. Additional biochemical measurements indicated that overexpression of the Ca 2+/calmodulin-binding kinase did not perturb other Ca 2+/calmodulin-dependent processes involving Ca2+/ calmodulin-dependent protein kinase II or the protein phosphatase calcineurin. Thus, increased myosin RLC phosphorylation per se does not cause cardiac hypertrophy and probably inhibits physiological and pathophysiological hypertrophy by contributing to enhanced contractile performance and efficiency.

Original languageEnglish (US)
Pages (from-to)19748-19756
Number of pages9
JournalJournal of Biological Chemistry
Volume283
Issue number28
DOIs
StatePublished - Jul 11 2008

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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