Low-dose Bis (Maltolato) Oxovanadium(IV) Attenuates Injuries In High Glucose-Treated Cardiac Cells And Diabetic Rat Hearts By Regulating Endoplasmic Reticulum Stress

Background: Diabetes is currently a serious threat to the health and quality of life of the people. Over half of the deaths ofdiabetic patients were caused by cardiovascular complications. How to protect cardiovascular function under high glucose environment is very important. As a common pathway of apoptosis, plays an important role in diabetic myocardial injury. Based on the ERS related molecular mechanism and signal transduction pathway regulation to attenuate myocardial cells injury may provide a new therapeutic target for the treatment of diabetic myocardial injury. Currently there is no effective medicine to prevent myocardial cells injury. Bis(maltolato) oxovandium(BMOV) as an organic vanadium complexes at high dose can inhibit ERS in islet cell but irritate gastrointestinal systemin animal model, which limited its potential clinic use.Our research investigatingif low dose BMOV can improve high glucose induced myocardial injury without causing gastrointestinal irritation.Objective: To investigatelow dose BMOV cardiomyocyte protectionon STZ treated rats, we measured ERS signal transduction protein and m RNA expression, Further in H9C2(2-1) cells, we proved BMOV can regulated the endoplasmic reticulum stress and protected the cardiomyocyte apoptosis in diabetic rats.Methods: The diabetic Wistarrats model was established by intraperitoneally injected of STZ, and the cell apoptosis was detected after different dose of BMOV treatment. We measureddprotein expression and the level of m RNA of the GRP-78, PERK, XBP-1, CHOP.We further using the H9C2(2-1) myocardial cell line to simulate the diabetic environment, after BMOV intervention to measure ERS related protein and to illustrate its cardiomyocytes protection role..Results: the study haveshown the apoptosis of STZ was decreased after treatment of BMOV in rats. Low-dose BMOV intervention reduced cardiomyocytes apoptosis, ERS initiation protein GRP-78 expression decreased, ers pathway protein expression of perk decreased, downstream apoptotic chop protein was significantly reduced, as well as the cell pro-survivalrelated protein XBP-1 expression. In the H9C2(2-1)cell experiment, BMOV can also regulatelevel of ERS response, decrease GRP-78 expression, down regulate PERK and apoptosis related CHOP protein, as well as the cell pro-survival related protein XBP-1 expression down.Conclusion: Both in vivo and in vitro study have shown that BMOW can inhibit hyperglycemic induced GRP78 protein high expression, inhibit PERK、CHOP、Caspase12 induced diabetic cardiomyocytes injury. Improve XBP-1 protein expression on cell level, although no similar results were being observed in animal studies.Together with rat blood glucose result,Low-dose BMOVcan inhibit ERS induced apoptosis without affecting blood glucose control and induced pro-survival protein expression.