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- W2052945454 abstract "Diabetes reduces myocardial contractility. Studies attribute this defect in part to a dysfunction of cardiac mitochondria. However, molecular mechanisms responsible for mitochondrial dysfunction during diabetes remain incompletely defined. The present study was designed to determine whether diabetes alter expression and activity of cardiac mitochondrial ryanodine receptor (mRyR). Type 1 diabetes was induced in male Sprague-Dawley rats using streptozotocin (STZ). Two and eight weeks after STZ injection, diabetic rats were sacrificed, hearts harvested, and cardiac mitochondria were purified using differential and Percoll gradient centrifugations. In Western blots, bottom and middle Percoll fractions from control hearts immuno-reacted with VDAC and COX IV, but not with SERCA2 antibodies. These fractions also contained a protein of Mw≈500kDa that immuno-reacted with RyR2 but not with RyR1 antibodies. Trypsin digestion followed by mass spectroscopic analysis revealed this high molecular weight protein to be RyR2 (mRyR2). After two weeks of diabetes, mRyR2 protein level in bottom fraction increased 1.8 fold, as was total [3H]ryanodine bound (11.9 ± 4.8 fmol [3H]ryanodine bound/mg protein for control vs 17.5 ± 2.0 fmol/mg protein for diabetic at 900μM Ca2+). After 8 weeks of diabetes, mRyR2 protein level remained elevated. Interestingly, the activity of mRyR2 as assessed from [3H]ryanodine bound increased 5-fold (from 46.9 ± 8.1 fmol/mg protein in control to 262.7 ± 40.1 fmol/mg protein at 200μM Ca2+). Two weeks of insulin-treatment initiated after 6 weeks of diabetes, normalized expression and activity of mRyR2 to near control values. These data are the first to show mRyR2 expression increases in heart during diabetes. This increase in expression of mRyR2 during diabetes could perturb mitochondrial Ca2+ homeostasis resulting in disrupting of ATP production and a reduction in myocyte function. (Supported in part by NIH grants to S-SS and KRB)" @default.
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- W2052945454 date "2009-02-01" @default.
- W2052945454 modified "2023-09-25" @default.
- W2052945454 title "Increased Levels Of Type 2 Ryanodine Receptor (RyR2) In Rat Heart Mitochondria During Diabetes" @default.
- W2052945454 doi "https://doi.org/10.1016/j.bpj.2008.12.499" @default.
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