The serine/threonine-protein kinase/endoribonuclease IRE1α protects the heart against pressure overload-induced heart failure

The Journal of Biological Chemistry
DeAnna SteigerYibin Wang

Abstract

Heart failure is associated with induction of endoplasmic reticulum (ER) stress and the unfolded protein response (UPR). The serine/threonine protein kinase/endoribonuclease IRE1α is a key protein in ER stress signal transduction. IRE1α activity can induce both protective UPR and apoptotic downstream signaling events, but the specific role for IRE1α activity in the heart is unknown. A major aim of this study was to characterize the specific contribution of IRE1α in cardiac physiology and pathogenesis. We used both cultured myocytes and a transgenic mouse line with inducible and cardiomyocyte-specific IRE1α overexpression as experimental models to achieve targeted IRE1α activation. IRE1α expression induced a potent but transient ER stress response in cardiomyocytes and did not cause significant effects in the intact heart under normal physiological conditions. Furthermore, the IRE1α-activated transgenic heart responding to pressure overload exhibited preserved function and reduced fibrotic area, associated with increased adaptive UPR signaling and with blunted inflammatory and pathological gene expression. Therefore, we conclude that IRE1α induces transient ER stress signaling and confers a protective effect against pressure ove...Continue Reading

References

Sep 25, 1991·Proceedings of the National Academy of Sciences of the United States of America·H A RockmanK R Chien
Oct 11, 2001·Proceedings of the National Academy of Sciences of the United States of America·P LiaoY Wang
Feb 21, 2003·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Brian G PetrichYibin Wang
Mar 4, 2003·Nature Reviews. Molecular Cell Biology·Lars Ellgaard, Ari Helenius
Dec 20, 2003·Cell Death and Differentiation·S Oyadomari, M Mori
Apr 9, 2004·The Journal of Biological Chemistry·Kezhong Zhang, Randal J Kaufman
May 12, 2004·Current Medicinal Chemistry·Earl R Stadtman
Aug 18, 2004·Molecular and Cellular Biology·Jaime D BlaisJohn C Bell
Sep 15, 2004·Journal of Chemical Neuroanatomy·Xiaohua ShenRandal J Kaufman
Sep 15, 2004·Journal of Chemical Neuroanatomy·Hisae KadowakiHidenori Ichijo
Dec 18, 2004·Mutation Research·Martin Schröder, Randal J Kaufman
Apr 5, 2005·Methods : a Companion to Methods in Enzymology·Amy S Lee
Dec 22, 2005·Physiological Genomics·Scherise MitchellYibin Wang
Dec 24, 2005·Apoptosis : an International Journal on Programmed Cell Death·R KimS Murakami
Jan 7, 2006·Cell Death and Differentiation·D LindholmL Korhonen
Feb 24, 2006·Genesis : the Journal of Genetics and Development·Tomo-O Ishikawa, Harvey R Herschman
Apr 18, 2006·American Journal of Physiology. Heart and Circulatory Physiology·Asim AzferPappachan E Kolattukudy
Jun 24, 2006·Circulation Research·Donna J ThueraufChristopher C Glembotski
Jul 25, 2006·Nature Medicine·Risto KerkeläThomas Force
Oct 4, 2006·Physiological Reviews·Stefan J Marciniak, David Ron
Oct 13, 2006·Molecular and Cellular Biology·Maiko OgataKazunori Imaizumi
Nov 10, 2007·Circulation Research·Christopher C Glembotski
Jan 15, 2008·Cell·David Ron, Stevan R Hubbard
Nov 26, 2008·Journal of Molecular and Cellular Cardiology·Alexandra R CookMetin Avkiran
Mar 31, 2009·Molecular Cell·Fernanda LisbonaClaudio Hetz
May 7, 2009·Proceedings of the National Academy of Sciences of the United States of America·Lingfang ZengQingbo Xu
Jun 16, 2009·Canadian Journal of Physiology and Pharmacology·Daniel Prins, Marek Michalak

❮ Previous
Next ❯

Citations

May 22, 2019·Current Topics in Medicinal Chemistry·Guangyu ZhangZhao V Wang
Aug 9, 2019·Current Topics in Medicinal Chemistry·Bingqian YanWei Fu
Nov 17, 2020·Frontiers in Cardiovascular Medicine·Namrita KaurWei Liu
Feb 24, 2021·Nature Reviews. Cardiology·Jun RenYingmei Zhang

❮ Previous
Next ❯

Related Concepts

Related Feeds

Adenoma, Islet Cell

Islet Cell Adenoma arises in the islet cells, which are insulin producing cells of the pancreas. These tumors can be either malignant or benign. Discover the latest research on Islet Cell Adenoma here.

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.