Involvement of Orai1 in tunicamycin-induced endothelial dysfunction

Endoplasmic reticulum (ER) stress is mediated by disturbance of Ca 2+ homeostasis.The store-operated calcium (SOC) channel is the primary Ca 2+ channel in non-excitable cells, but its participation in agent-induced ER stress is not clear.In this study, the effects of tunicamycin on Ca 2+ influx in human umbilical vein endothelial cells (HUVECs) were observed with the fluorescent probe Fluo-4 AM.The effect of tunicamycin on the expression of the unfolded protein response (UPR)-related proteins BiP and CHOP was assayed by western blotting with or without inhibition of Orai1.Tunicamycin induced endothelial dysfunction by activating ER stress.Orai1 expression and the influx of extracellular Ca 2+ in HUVECs were both upregulated during ER stress.The SOC channel inhibitor SKF96365 reversed tunicamycin-induced endothelial cell dysfunction by inhibiting ER stress.Regulation of tunicamycin-induced ER stress by Orai1 indicates that modification of Orai1 activity may have therapeutic value for conditions with ER stress-induced endothelial dysfunction.