TDCPP protects cardiomyocytes from hypoxia-reoxygenation injury induced apoptosis through mitigating calcium overload and promotion GSK-3β phosphorylation

Abstract

TDCPP , Tris (1, 3-dichloro-2-propyl) phosphate belongs to a group of chemicals known as triester organophosphate flame retardants , It can alter calcium homeostasis at much lower concentrations in normal conditions, but the mechanism is unclear till now. Calcium overload is a leading cause of apoptosis in myocardial ischemia/reperfusion (I/R) injury , thus how to mitigate Ca 2+ -overload is deserved to be investigated. We therefore hypothesized that TDCPP could attenuate cardiomyocytes apoptosis in I/R injury. H/R (hypoxia/reoxygenation) experiments in vitro were used to simulate in vivo I/R injury. The present study aimed to explore the potential effect of TDCPP in cardiomyocytes after H/R injury, Ca 2+ imaging technique was used to explore SOCE(store-operated calcium entry) and Ca 2+ -overload levels, western blot technique was used to explore the potential target, the cell morphology, cell viability and mitochondrial membrane potential were also detected. The results have shown that: TDCPP could decrease SOCE, restore H9c2 cell viability , mitigate Ca 2+ -overload in H/R injury and reduce the mitochondrial membrane potential. Furthermore, TDCPP decreased STIM1 expression and promoted GSK3β phosphorylation. Collectively, for the first time, this study suggest the antiapoptosis roles of TDCPP in H/R injury are via mitigation Ca 2+ -overload and promoting GSK-3β phosphorylation.