Major contribution of the 3/6/7 class of TRPC channels to myocardial ischemia/reperfusion and cellular hypoxia/reoxygenation injuries

Proceedings of the National Academy of Sciences of the United States of America
Xiju HeYanhong Liao

Abstract

The injury phase after myocardial infarcts occurs during reperfusion and is a consequence of calcium release from internal stores combined with calcium entry, leading to cell death by apoptopic and necrotic processes. The mechanism(s) by which calcium enters cells has(ve) not been identified. Here, we identify canonical transient receptor potential channels (TRPC) 3 and 6 as the cation channels through which most of the damaging calcium enters cells to trigger their death, and we describe mechanisms activated during the injury phase. Working in vitro with H9c2 cardiomyoblasts subjected to 9-h hypoxia followed by 6-h reoxygenation (H/R), and analyzing changes occurring in areas-at-risk (AARs) of murine hearts subjected to a 30-min ischemia followed by 24-h reperfusion (I/R) protocol, we found: (i) that blocking TRPC with SKF96365 significantly ameliorated damage induced by H/R, including development of the mitochondrial permeability transition and proapoptotic changes in Bcl2/BAX ratios; and (ii) that AAR tissues had increased TUNEL+ cells, augmented Bcl2/BAX ratios, and increased p(S240)NFATc3, p(S473)AKT, p(S9)GSK3β, and TRPC3 and -6 proteins, consistent with activation of a positive-feedback loop in which calcium entering thr...Continue Reading

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Citations

Sep 25, 2017·Frontiers in Cardiovascular Medicine·Takuro Numaga-TomitaMotohiro Nishida
Sep 3, 2018·Molecular and Cellular Biochemistry·Weishan ZhangYanhong Liao
Feb 26, 2019·Evidence-based Complementary and Alternative Medicine : ECAM·Yuan GaoMing-Jun Zhu
Apr 8, 2020·Frontiers in Aging Neuroscience·Lu LiuShengmei Zhu
Mar 19, 2019·Frontiers in Physiology·Debora FalcónTarik Smani
Nov 6, 2018·Regenerative Engineering and Translational Medicine·Timothy Chen, Gordana Vunjak-Novakovic
May 8, 2020·Oxidative Medicine and Cellular Longevity·Xiuya YaoDan Liu
Mar 12, 2020·Frontiers in Cardiovascular Medicine·Hairuo WenLai-Hua Xie
Jul 25, 2021·International Journal of Molecular Sciences·Natthaphat Siri-AngkulJudith K Gwathmey
Jul 27, 2021·Frontiers in Molecular Biosciences·Xin HouYanhong Liao
Sep 10, 2021·Annual Review of Pharmacology and Toxicology·Robin S BonPiruthivi Sukumar

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