Dysfunction of cardiac ryanodine receptors in the metabolic syndrome

U. Deniz Dincer, Alberto Araiza, Jarrod D. Knudson, Chun Hong Shao, Keshore R. Bidasee, Johnathan Tune

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

This study examined the hypothesis that the prediabetic metabolic syndrome alters expression, phosphorylation state and binding affinity of cardiac RyR2. Real-time PCR and Western blot analysis were used to assess mRNA and protein expression in the left ventricle, right ventricle and right atrium from control (n = 5) and chronically high-fat-fed (n = 5) dogs with the metabolic syndrome. Functional integrity of RyR2 was assessed by RyR2-Ser2809 phosphorylation and the receptor's ability to bind [3H]ryanodine. We found that RyR2 phosphorylation at Ser2809 was significantly elevated in right and left ventricle from high-fat-fed dogs compared to normal control dogs. This hyperphosphorylation was associated with a decrease in RyR2 binding affinity in right and left ventricle (high-fat diet = 80.2 and 90.5 fmol/mg protein vs. control = 243.6 and 200.9 fmol/mg protein, respectively) and a decrease in cardiac index in exercising dogs. RyR2 phosphorylation at Ser2809 and RyR2 binding affinity were not altered in the right atria of high-fat-fed dogs. In addition, no significant differences in cardiac RyR2 mRNA or protein expression were noted between groups. These data suggest that alterations in RyR2 could be an important mechanism of early cardiac dysfunction in obesity and insulin resistance.

Original languageEnglish (US)
Pages (from-to)108-114
Number of pages7
JournalJournal of Molecular and Cellular Cardiology
Volume41
Issue number1
DOIs
StatePublished - Jul 2006
Externally publishedYes

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Ryanodine Receptor Calcium Release Channel
Heart Ventricles
Dogs
Phosphorylation
Fats
Heart Atria
Proteins
Ryanodine
Messenger RNA
High Fat Diet
Insulin Resistance
Real-Time Polymerase Chain Reaction
Obesity
Western Blotting

Keywords

  • "Leaky" RyR
  • Heart
  • Prediabetic metabolic syndrome
  • Ryanodine receptor
  • RyR-Ser phosphorylation

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

Cite this

Dysfunction of cardiac ryanodine receptors in the metabolic syndrome. / Dincer, U. Deniz; Araiza, Alberto; Knudson, Jarrod D.; Shao, Chun Hong; Bidasee, Keshore R.; Tune, Johnathan.

In: Journal of Molecular and Cellular Cardiology, Vol. 41, No. 1, 07.2006, p. 108-114.

Research output: Contribution to journalArticle

Dincer, U. Deniz ; Araiza, Alberto ; Knudson, Jarrod D. ; Shao, Chun Hong ; Bidasee, Keshore R. ; Tune, Johnathan. / Dysfunction of cardiac ryanodine receptors in the metabolic syndrome. In: Journal of Molecular and Cellular Cardiology. 2006 ; Vol. 41, No. 1. pp. 108-114.
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