Journal
REDOX BIOLOGY
Volume 34, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.redox.2020.101559
Keywords
Succinate dehydrogenase; Glutamine synthetase; Oxidative stress; Proteasomal degradation; Glutamate excitotoxicity; Baicalin
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Funding
- Double First-Class University [CPU2018GF07]
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Background: Many neuroprotective approaches targeting neurons in animal models fail to provide bene fits for the treatment of ischemic stroke in clinic and glial cells have become the targets in some basic studies. Baicalin has neuroprotective e ffects 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 de- privation/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 oxi- dative 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 e ffective strategy to prevent neuronal injury in acute ischemic stroke.
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