Oxidative Stress Plays Important Role on Cardiac Ryanodine Receptor Calcium Release Channels in Diabetic Rats

Abstract

Reactive oxygen species play an important role in the development of diabetic cardiomyopathy due to alteration of Ca2+ signaling via changes in critical processes that regulate contractile activity of heart. Since these defects result partially from a dysfunction of cardiac ryanodine receptor calcium release channels (RyR2s), the present study was aimed to examine whether protective effect of in vivo administration of sodium selenate on contractile activity of heart from diabetic rats via affecting the hyperphosphorylation level of RyR2s and their a number of accessory proteins. Selenium normalized prolonged action potential duration and improved depressed tension obtained with electrically stimulated papillary muscle from diabetic rat hearts. Moreover, selenium reduced the increased oxidative stress and depressed oxtioxidant defence system in both plasma and heart tissue of diabetic rats. Western-blot data indicated that sodium selenate-treatment prevented markedly hyperphosphorylation of RyR2s, and activations of PKA, CaMKII and NF-κB as well as reduction in Trx level of the diabetic rat hearts. In the present study, we demonstrated that the mechanisms responsible for the cardioprotective effects of sodium selenate in the diabetic myocardium include preservation of oxidative stress-induced hyperphosphorylation and activation of Ca2+ signaling proteins, as well as with a normalization of NF-κB. Therefore, such an observation provides evidences for a potential therapeutic usage of selenium compounds in the amelioration of cardiovascular disorders in diabetes (Supported by TUBITAK SBAG-107S304).