Abstract
In this study, we tested the hypotheses that 1) diabetes-induced disturbances in cardiac my-ATPase activity would be attributed to not only myosin heavy chain (MHC) isoform transitions, but also reduced amounts in MHC protein; and 2) if diabetes results in declines in the MHC protein content, this change would relate to oxidative damage to MHC. Diabetes was induced by a single intraperitoneal injection of streptozotocin. After 6 weeks of injection, the left ventricles were excised for mechanical and biochemical analyses. Peak twitch tension and the rate of force development in papillary muscles were decreased by 23.4% and 34.1%, respectively. A 33.5% reduction in myofibrillar ATPase activity occurred in conjunction with a 9.5% decrease in MHC protein as well as MHC isoform transitions towards a slower phenotype. The decreased MHC content was not accompanied by elevations in carbonyl groups present in MHC. Whole muscle analyses indicated that the contents of malondialdehyde and reduced glutathione were elevated. These results suggest that decreases in the MHC content may be associated, at least in part, with a diabetes-related inactivation of cardiac my-ATPase and may not be due to accumulation of oxidative damage to protein.
Highlights
The prevalence of diabetes mellitus is growing rapidly from 170 million in 2000 to an estimated 366 million in 2030 [1]
These results suggest that decreases in the myosin heavy chain (MHC) content may be associated, at least in part, with a diabetes-related inactivation of cardiac my-ATPase and may not be due to accumulation of oxidative damage to protein
It is well known that the prime determinant of the contractile properties, the maximum shortening velocity, in the muscle cell is the catalytic activity of myofibrillar ATPase which resides in the head region of myosin heavy chain (MHC) [3]
Summary
The prevalence of diabetes mellitus is growing rapidly from 170 million in 2000 to an estimated 366 million in 2030 [1]. Diabetes mellitus can induce abnormalities in ventricular muscle independent of changes in blood pressure and coronary artery disease, a condition called “diabetic cardiomyopathy”. It is well known that the prime determinant of the contractile properties, the maximum shortening velocity, in the muscle cell is the catalytic activity of myofibrillar ATPase (my-ATPase) which resides in the head region of myosin heavy chain (MHC) [3]. Diabetic cardiomyopathy has been demonstrated to be accompa nied by the downregulation of α-MHC together with the upregulation of β-MHC, resulting in the decreased my-ATPase activity [6]. The deteriorations in shortening velocity and power output that occur in diabetic heart are explained, in part, by a shift in MHC towards a slower phenotype. The maximum shortening velocity in diabetic cardiomyocyte declines more than would be expected from MHC isoform transitions [6], suggesting that other mechanisms are involved
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