Reduced FAK-STAT3 signaling contributes to ER stress-induced mitochondrial dysfunction and death in endothelial cells

Cellular Signalling
Kalpita BanerjeeTheo Hagg

Abstract

Excessive endoplasmic reticulum (ER) stress leads to cell loss in many diseases, e.g., contributing to endothelial cell loss after spinal cord injury. Here, we determined whether ER stress-induced mitochondrial dysfunction could be explained by interruption of the focal adhesion kinase (FAK)-mitochondrial STAT3 pathway we recently discovered. ER stress was induced in brain-derived mouse bEnd5 endothelial cells by thapsigargin or tunicamycin and caused apoptotic cell death over a 72h period. In concert, ER stress caused mitochondrial dysfunction as shown by reduced bioenergetic function, loss of mitochondrial membrane potential and increased mitophagy. ER stress caused a reduction in mitochondrial phosphorylated S727-STAT3, known to be important for maintaining mitochondrial function. Normal activation or phosphorylation of the upstream cytoplasmic FAK was also reduced, through mechanisms that involve tyrosine phosphatases and calcium signaling, as shown by pharmacological inhibitors, bisperoxovanadium (bpV) and 2-aminoethoxydiphenylborane (APB), respectively. APB mitigated the reduction in FAK and STAT3 phosphorylation, and improved endothelial cell survival caused by ER stress. Transfection of cells rendered null for STAT3 usi...Continue Reading

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Citations

Sep 8, 2018·Journal of Cellular Physiology·Junqin ShengJianxun Feng
May 10, 2019·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Dong-Yeon KimWon-Ha Lee
Jul 16, 2020·Experimental Biology and Medicine·Longfei PanHongyan Tian
May 16, 2018·Cellular & Molecular Biology Letters·Xisong Wang, Qing Song
Jun 20, 2019·International Journal of Molecular Sciences·Lingyue HuaNianlong Yan
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May 26, 2020·Life Sciences·Qidong CaoChunli Song
Apr 23, 2021·Journal of Cellular Physiology·Wangrui LeiYang Yang
Jul 20, 2018·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Yan WangQiang Liu

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