Involvement of Orai1 in tunicamycin-induced endothelial dysfunction.
10.4196/kjpp.2019.23.2.95
- Author:
Hui YANG
1
;
Yumei XUE
;
Sujuan KUANG
;
Mengzhen ZHANG
;
Jinghui CHEN
;
Lin LIU
;
Zhixin SHAN
;
Qiuxiong LIN
;
Xiaohong LI
;
Min YANG
;
Hui ZHOU
;
Fang RAO
;
Chunyu DENG
Author Information
1. Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial Key Laboratory of Clinical Pharmacology, Guangzhou, Guangdong 510080, China. chunyudeng@126.com, raofang@medmail.com.cn
- Publication Type:Original Article
- Keywords:
Endoplasmic reticulum stress;
Endothelial cells;
Orai1;
Store-operated calcium channel
- MeSH:
Blotting, Western;
Calcium;
Endoplasmic Reticulum;
Endoplasmic Reticulum Stress;
Endothelial Cells;
Homeostasis;
Human Umbilical Vein Endothelial Cells;
Tunicamycin;
Unfolded Protein Response
- From:The Korean Journal of Physiology and Pharmacology
2019;23(2):95-102
- CountryRepublic of Korea
- Language:English
-
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.
