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- W2058370904 abstract "To examine whether excessive protein O -GlcNAcylation plays a role in the dysfunction of the diabetic heart, we delivered adenovirus expressing O -GlcNAcase (Adv-GCA) into the myocardium of STZ-induced diabetic mice. Our results indicated that excessive cellular O -GlcNAcylation exists in the diabetic heart, and that in vivo GCA overexpression reduces overall cellular O -GlcNAcylation. Myocytes isolated from diabetic hearts receiving Adv-GCA exhibited improved calcium transients with a significantly shortened T decay ( P <0.01) and increased sarcoplasmic reticulum Ca 2+ load ( P <0.01). These myocytes also demonstrated improved contractility including a significant increase in +dL/dt and −dL/dt and greater fractional shortening as measured by edge detection ( P <0.01). In isolated perfused hearts, developed pressure and −dP/dt were significantly improved in diabetic hearts receiving Adv-GCA ( P <0.05). These hearts also exhibited a 40% increase in SERCA2a expression. Phospholamban protein expression was reduced 50%, but the phosphorylated form was increased 2-fold in the diabetic hearts receiving Adv-GCA. We conclude that excess O -GlcNAcylation in the diabetic heart contributes to cardiac dysfunction, and reducing this excess cellular O -GlcNAcylation has beneficial effects on calcium handling and diabetic cardiac function." @default.
- W2058370904 created "2016-06-24" @default.
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- W2058370904 date "2005-05-13" @default.
- W2058370904 modified "2023-10-16" @default.
- W2058370904 title "Adenovirus-Mediated Overexpression of <i>O</i> -GlcNAcase Improves Contractile Function in the Diabetic Heart" @default.
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- W2058370904 doi "https://doi.org/10.1161/01.res.0000165478.06813.58" @default.
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