Inhibition of TGFβ-activated Protein Kinase 1 Ameliorates Myocardial Ischaemia/reperfusion Injury Via Endoplasmic Reticulum Stress Suppression

Overview

Journal J Cell Mol Med

Specialties Cell Biology
Molecular Biology

Date 2020 May 8

PMID 32378287

Citations 13

Authors

Jingjing Zeng

Qike Jin

Yongxue Ruan

Changzheng Sun

Guangyu Xu

Maoping Chu

Kangting Ji

Lianpin Wu

Lei Li

Affiliations

Soon will be listed here.

Abstract

Transforming growth factor β-activated protein kinase 1 (TAK1) involves in various biological responses and is a key regulator of cell death. However, the role of TAK1 on acute myocardial ischaemia/reperfusion (MI/R) injury is unknown. We observed that TAK1 activation increased significantly after MI/R and hypoxia/reoxygenation (H/R), and we hypothesized that TAK1 has an important role in MI/R injury. Mice (TAK1 inhibiting by 5Z-7-oxozeaenol or silencing by AAV9 vector) were exposed to MI/R injury. Primary cardiomyocytes (TAK1 silencing by siRNA; and overexpressing TAK1 by adenovirus vector) were used to induce H/R injury model in vitro. Inhibition of TAK1 significantly decreased MI/R-induced myocardial infarction area, reduced cell death and improved cardiac function. Mechanistically, TAK1 silencing suppressed MI/R-induced myocardial oxidative stress and attenuated endoplasmic reticulum (ER) stress both in vitro and in vivo. In addition, the inhibition of ROS by NAC partially reversed the damage of TAK1 in vitro. Our study presents the first direct evidence that inhibition of TAK1 mitigated MI/R injury, and TAK1 mediated ROS/ER stress/apoptosis signal pathway is important for the pathogenesis of MI/R injury.

Citing Articles

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