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Involvement of Orai1 in tunicamycin-induced endothelial dysfunction.

ABSTRACT: Endoplasmic reticulum (ER) stress is mediated by disturbance of Ca2+ homeostasis. The store-operated calcium (SOC) channel is the primary Ca2+ channel in non-excitable cells, but its participation in agent-induced ER stress is not clear. In this study, the effects of tunicamycin on Ca2+ 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 Ca2+ 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.

SUBMITTER: Yang H

PROVIDER: S-EPMC6384200 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Involvement of Orai1 in tunicamycin-induced endothelial dysfunction.

Yang Hui H Xue Yumei Y Kuang Sujuan S Zhang Mengzhen M Chen Jinghui J Liu Lin L Shan Zhixin Z Lin Qiuxiong Q Li Xiaohong X Yang Min M Zhou Hui H Rao Fang F Deng Chunyu C

The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology 20190215 2

Endoplasmic reticulum (ER) stress is mediated by disturbance of Ca2+ homeostasis. The store-operated calcium (SOC) channel is the primary Ca2+ channel in non-excitable cells, but its participation in agent-induced ER stress is not clear. In this study, the effects of tunicamycin on Ca2+ 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 r ...[more]

PMID: 30820153

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Involvement of Orai1 in tunicamycin-induced endothelial dysfunction.

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Involvement of Orai1 in tunicamycin-induced endothelial dysfunction.

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