GSK-126 Attenuates Cell Apoptosis in Ischemic Brain Injury by Modulating the EZH2-H3K27me3-Bcl2l1 Axis

Overview

Journal Mol Neurobiol

Specialties Molecular Biology
Neurology

Date 2023 Nov 22

PMID 37989985

Authors

Tai Zhou

Lei Zhang

Li He

Yan Lan

Lei Ding

Li Li

Zhongcheng Wang

Affiliations

Soon will be listed here.

Abstract

Whether epigenetic modifications participate in the cell apoptosis after ischemic stroke remains unclear. Histone 3 tri-methylation at lysine 27 (H3K27me3) is a histone modification that leads to gene silencing and is involved in the pathogenesis of ischemic stroke. Since the expression of many antiapoptotic genes is inhibited in the ischemic brains, here we aimed to offer an epigenetic solution to cell apoptosis after stroke by reversing H3K27me3 levels after ischemia. GSK-126, a specific inhibitor of enhancer of zeste homolog 2 (EZH2), significantly decreased H3K27me3 levels and inhibited middle cerebral artery occlusion (MCAO) induced and oxygen glucose deprivation (OGD) induced cell apoptosis. Moreover, GSK-126 attenuated the apoptosis caused by oxidative stress, excitotoxicity, and excessive inflammatory responses in vitro. The role of H3K27me3 in regulating of the expression of the antiapoptotic molecule B cell lymphoma-2 like 1 (Bcl2l1) explained the antiapoptotic effect of GSK-126. In conclusion, we found that GSK-126 could effectively protect brain cells from apoptosis after cerebral ischemia, and this role of GSK-126 is closely related to an axis that regulates Bcl2l1 expression, beginning with the regulation of EZH2-dependent H3K27me3 modification.

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