Carbonylation of myosin heavy chains in rat heart during diabetes

Chun Hong Shao, George J. Rozanski, Ryoji Nagai, Frank E. Stockdale, Kaushik P. Patel, Mu Wang, Jaipaul Singh, William G. Mayhan, Keshore R. Bidasee

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

Cardiac inotropy progressively declines during diabetes mellitus. To date, the molecular mechanisms underlying this defect remain incompletely characterized. This study tests the hypothesis that ventricular myosin heavy chains (MHC) undergo carbonylation by reactive carbonyl species (RCS) during diabetes and these modifications contribute to the inotropic decline. Male Sprague-Dawley rats were injected with streptozotocin (STZ). Fourteen days later the animals were divided into two groups: one group was treated with the RCS blocker aminoguanidine for 6 weeks, while the other group received no treatment. After 8 weeks of diabetes, cardiac ejection fraction, fractional shortening, left ventricular pressure development (+dP/dt) and myocyte shortening were decreased by 9%, 16%, 34% and 18%, respectively. Ca2+- and Mg2+-actomyosin ATPase activities and peak actomyosin syneresis were also reduced by 35%, 28%, and 72%. MHC-α to MHC-β ratio was 12:88. Mass spectrometry and Western blots revealed the presence of carbonyl adducts on MHC-α and MHC-β. Aminoguanidine treatment did not alter MHC composition, but it blunted formation of carbonyl adducts and decreases in actomyosin Ca2+-sensitive ATPase activity, syneresis, myocyte shortening, cardiac ejection fraction, fractional shortening and +dP/dt induced by diabetes. From these new data it can be concluded that in addition to isozyme switching, modification of MHC by RCS also contributes to the inotropic decline seen during diabetes.

Original languageEnglish (US)
Pages (from-to)205-217
Number of pages13
JournalBiochemical Pharmacology
Volume80
Issue number2
DOIs
StatePublished - Jul 2010

Keywords

  • Carbonyl adducts
  • Contractility
  • Diabetes
  • Myosin heavy chain
  • Rat
  • Reactive carbonyl species
  • Streptozotocin

ASJC Scopus subject areas

  • Pharmacology
  • Biochemistry

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