Baicalin Combats Glutamate Excitotoxicity Via Protecting Glutamine Synthetase from ROS-induced 20S Proteasomal Degradation

Overview

Journal Redox Biol

Specialties Biology
Cell Biology
Endocrinology

Date 2020 May 31

PMID 32473460

Citations 45

Authors

Xianrui Song

Zixuan Gong

Kaili Liu

Junping Kou

Baolin Liu

Kang Liu

Affiliations

Soon will be listed here.

Abstract

Background: Many neuroprotective approaches targeting neurons in animal models fail to provide benefits for the treatment of ischemic stroke in clinic and glial cells have become the targets in some basic studies. Baicalin has neuroprotective effects but the mechanisms related to glial cells are not revealed. This study investigated whether and how baicalin can combat excitotoxicity via protecting the functions of astrocytes in early stage of ischemia/reperfusion (I/R) insult by focusing on glutamine synthetase (GS).

Experimental Approach: The role of baicalin was explored in primary astrocytes exposed to oxygen-glucose deprivation/reperfusion (OGD/R) and rats subjected to middle cerebral artery occlusion/reperfusion (MCAO/R).

Key Results: Mitochondrial succinate dehydrogenase (SDH) activation led to an excessive production of reactive oxygen species (ROS) via reverse electron transport (RET) under conditions of OGD/R or I/R, which increased the carbonylation and proteasomal degradation of GS in astrocytes. Treatment of baicalin decreased the oxidative stress mediated by SDH and reduced the subsequent loss of GS. This effect increased the glutamate disposal by astrocytes and protected neurons from excitotoxicity in response to I/R insults.

Conclusions And Implications: Baicalin inactivated SDH to suppress ROS production and protected GS protein stability against oxidative stress, contributing to the improvement of the glutamate disposal and decrease in excitotoxicity. These results suggest that protection of GS stability in astrocytes might be an effective strategy to prevent neuronal injury in acute ischemic stroke.

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