Baicalin combats glutamate excitotoxicity via protecting glutamine synthetase from ROS-induced 20S proteasomal degradation
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...
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doaj-9684f71e6532468888b284a7aa67919e2020-11-25T03:12:35ZengElsevierRedox Biology2213-23172020-07-0134101559Baicalin combats glutamate excitotoxicity via protecting glutamine synthetase from ROS-induced 20S proteasomal degradationXianrui Song0Zixuan Gong1Kaili Liu2Junping Kou3Baolin Liu4Kang Liu5Department of Pharmacology of Chinese Materia Medica, School of Traditional Chinese Pharmacy, China Pharmaceutical University, 639 Longmian Road, Nanjing, 211198, ChinaDepartment of Pharmacology of Chinese Materia Medica, School of Traditional Chinese Pharmacy, China Pharmaceutical University, 639 Longmian Road, Nanjing, 211198, ChinaDepartment of Pharmacology of Chinese Materia Medica, School of Traditional Chinese Pharmacy, China Pharmaceutical University, 639 Longmian Road, Nanjing, 211198, ChinaDepartment of Pharmacology of Chinese Materia Medica, School of Traditional Chinese Pharmacy, China Pharmaceutical University, 639 Longmian Road, Nanjing, 211198, China; Jiangsu Key Laboratory of TCM Evaluation and Translational Research, School of Traditional Chinese Pharmacy, China Pharmaceutical University, 639 Longmian Road, Nanjing, 211198, ChinaDepartment of Pharmacology of Chinese Materia Medica, School of Traditional Chinese Pharmacy, China Pharmaceutical University, 639 Longmian Road, Nanjing, 211198, China; Jiangsu Key Laboratory of TCM Evaluation and Translational Research, School of Traditional Chinese Pharmacy, China Pharmaceutical University, 639 Longmian Road, Nanjing, 211198, ChinaDepartment of Pharmacology of Chinese Materia Medica, School of Traditional Chinese Pharmacy, China Pharmaceutical University, 639 Longmian Road, Nanjing, 211198, China; Jiangsu Key Laboratory of TCM Evaluation and Translational Research, School of Traditional Chinese Pharmacy, China Pharmaceutical University, 639 Longmian Road, Nanjing, 211198, China; Corresponding author. Department of Pharmacology of Chinese Materia Medica, School of Traditional Chinese Pharmacy, China Pharmaceutical University, 639 Longmian Road, Nanjing, 211198, China.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.http://www.sciencedirect.com/science/article/pii/S2213231720302226Succinate dehydrogenaseGlutamine synthetaseOxidative stressProteasomal degradationGlutamate excitotoxicityBaicalin |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Xianrui Song Zixuan Gong Kaili Liu Junping Kou Baolin Liu Kang Liu |
spellingShingle |
Xianrui Song Zixuan Gong Kaili Liu Junping Kou Baolin Liu Kang Liu Baicalin combats glutamate excitotoxicity via protecting glutamine synthetase from ROS-induced 20S proteasomal degradation Redox Biology Succinate dehydrogenase Glutamine synthetase Oxidative stress Proteasomal degradation Glutamate excitotoxicity Baicalin |
author_facet |
Xianrui Song Zixuan Gong Kaili Liu Junping Kou Baolin Liu Kang Liu |
author_sort |
Xianrui Song |
title |
Baicalin combats glutamate excitotoxicity via protecting glutamine synthetase from ROS-induced 20S proteasomal degradation |
title_short |
Baicalin combats glutamate excitotoxicity via protecting glutamine synthetase from ROS-induced 20S proteasomal degradation |
title_full |
Baicalin combats glutamate excitotoxicity via protecting glutamine synthetase from ROS-induced 20S proteasomal degradation |
title_fullStr |
Baicalin combats glutamate excitotoxicity via protecting glutamine synthetase from ROS-induced 20S proteasomal degradation |
title_full_unstemmed |
Baicalin combats glutamate excitotoxicity via protecting glutamine synthetase from ROS-induced 20S proteasomal degradation |
title_sort |
baicalin combats glutamate excitotoxicity via protecting glutamine synthetase from ros-induced 20s proteasomal degradation |
publisher |
Elsevier |
series |
Redox Biology |
issn |
2213-2317 |
publishDate |
2020-07-01 |
description |
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. |
topic |
Succinate dehydrogenase Glutamine synthetase Oxidative stress Proteasomal degradation Glutamate excitotoxicity Baicalin |
url |
http://www.sciencedirect.com/science/article/pii/S2213231720302226 |
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