Inhibition of Store-Operated Calcium Entry Protects Endothelial Progenitor Cells from H(2)O(2)-Induced Apoptosis

Store-operated calcium entry (SOCE), a major mode of extracellular calcium entry, plays roles in a variety of cell activities. Accumulating evidence indicates that the intracellular calcium ion concentration and calcium signaling are critical for the responses induced by oxidative stress. The present study was designed to investigate the potential effect of SOCE inhibition on H(2)O(2)-induced apoptosis in endothelial progenitor cells (EPCs), which are the predominant cells involved in endothelial repair. The results showed that H(2)O(2)-induced EPC apoptosis was reversed by SOCE inhibition induced either using the SOCE antagonist ML-9 or via silencing of stromal interaction molecule 1 (STIM1), a component of SOCE. Furthermore, SOCE inhibition repressed the increases in intracellular reactive oxygen species (ROS) levels and endoplasmic reticulum (ER) stress and ameliorated the mitochondrial dysfunction caused by H(2)O(2). Our findings provide evidence that SOCE inhibition exerts a protective effect on EPCs in response to oxidative stress induced by H(2)O(2) and may serve as a potential therapeutic strategy against vascular endothelial injury.