The unfolded protein response in ischemic heart disease

Journal of Molecular and Cellular Cardiology
Xiaoding WangZhao V Wang

Abstract

Ischemic heart disease is a severe stress condition that causes extensive pathological alterations and triggers cardiac cell death. Accumulating evidence suggests that the unfolded protein response (UPR) is strongly induced by myocardial ischemia. The UPR is an evolutionarily conserved cellular response to cope with protein-folding stress, from yeast to mammals. Endoplasmic reticulum (ER) transmembrane sensors detect the accumulation of unfolded proteins and stimulate a signaling network to accommodate unfolded and misfolded proteins. Distinct mechanisms participate in the activation of three major signal pathways, viz. protein kinase RNA-like ER kinase, inositol-requiring protein 1, and activating transcription factor 6, to transiently suppress protein translation, enhance protein folding capacity of the ER, and augment ER-associated degradation to refold denatured proteins and restore cellular homeostasis. However, if the stress is severe and persistent, the UPR elicits inflammatory and apoptotic pathways to eliminate terminally affected cells. The ER is therefore recognized as a vitally important organelle that determines cell survival or death. Recent studies indicate the UPR plays critical roles in the pathophysiology of i...Continue Reading

Citations

Sep 1, 2018·Channels·Man Liu, Samuel C Dudley
Jun 13, 2019·Journal of the American Heart Association·Diem H Tran, Zhao V Wang
Aug 7, 2019·Acta Physiologica·Juan Ignacio Elio MariángeloCecilia Mundiña-Weilenmann
Aug 31, 2019·EMBO Molecular Medicine·Andrea GrundJoerg Heineke
Dec 4, 2019·Cell Death & Disease·Myong-Ho JeongJong-Sun Kang
Apr 24, 2020·Physiological Reports·Michael W StonerJanet R Manning
Oct 1, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Ning ZhangKeshu Xu
May 22, 2019·Current Topics in Medicinal Chemistry·Guangyu ZhangZhao V Wang
Aug 9, 2019·Current Topics in Medicinal Chemistry·Bingqian YanWei Fu
Feb 6, 2020·Frontiers in Cardiovascular Medicine·Adrian ArrietaChristopher C Glembotski
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Apr 24, 2020·Frontiers in Physiology·Christopher C GlembotskiWinston T Stauffer
Oct 17, 2020·Liver International : Official Journal of the International Association for the Study of the Liver·Yi YangYuxian Shen
Feb 24, 2021·Nature Reviews. Cardiology·Jun RenYingmei Zhang
Jul 2, 2021·Frontiers in Cardiovascular Medicine·Nisha WangLifang Yang

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