title: Dysfunction of cardiac ryanodine receptors in the metabolic syndrome.
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.
authors.affiliation: Department of Physiology, Louisiana State University Health Sciences Center, 1901 Perdido St., New Orleans, LA 70112, USA. udincer@iupui.edu
authors.forename: U Deniz
authors.initials: UD
authors.lastname: Dincer
authors.forename: Alberto
authors.initials: A
authors.lastname: Araiza
authors.forename: Jarrod D
authors.initials: JD
authors.lastname: Knudson
authors.forename: Chun Hong
authors.initials: CH
authors.lastname: Shao
authors.forename: Keshore R
authors.initials: KR
authors.lastname: Bidasee
authors.forename: Johnathan D
authors.initials: JD
authors.lastname: Tune
mesh_terms: D000818:Animals; D021961:Cell Membrane Structures / Q000378:metabolism; D004285:Dogs; D005260:Female; D008297:Male; D024821:Metabolic Syndrome / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism; D010766:Phosphorylation; D010805:Physical Conditioning, Animal; D012433:Ryanodine / Q000378:metabolism; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics / Q000378:metabolism*; D012694:Serine / Q000378:metabolism
chemical_list: D019837:Ryanodine Receptor Calcium Release Channel; D012433:Ryanodine; D012694:Serine