Preserving mitochondrial function by inhibiting GRP75 ameliorates neuron injury under ischemic stroke

Wen,Bin; Xu,Kai; Huang,Rui; Jiang,Teng; Wang,Jian; Chen,Jiehui; Chen,Juan; He,Benhong

doi:10.3892/mmr.2022.12681

Preserving mitochondrial function by inhibiting GRP75 ameliorates neuron injury under ischemic stroke

Authors:
- Bin Wen
- Kai Xu
- Rui Huang
- Teng Jiang
- Jian Wang
- Jiehui Chen
- Juan Chen
- Benhong He
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Affiliations: Department of Biochemistry and Molecular Biology, School of Basic Medicine and the Collaborative Innovation Center for Brain Science, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China, Department of Cardiovascular Medicine, Lichuan People's Hospital, Lichuan, Hubei 445400, P.R. China, Department of Biochemistry and Molecular Biology, School of Basic Medicine and the Collaborative Innovation Center for Brain Science, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China
Published online on: March 15, 2022 https://doi.org/10.3892/mmr.2022.12681
Article Number: 165
Copyright : © Wen et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY 4.0].

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Abstract

Ischemic stroke is a life‑threatening disease, which is closely related to neuron damage during ischemia. Mitochondrial dysfunction is essentially involved in the pathophysiological process of ischemic stroke. Mitochondrial calcium overload contributes to the development of mitochondrial dysfunction. However, the underlying mechanisms of mitochondrial calcium overload are far from being fully revealed. In the present study, middle cerebral artery obstruction (MCAO) was performed in vivo and oxygen and glucose deprivation (OGD) in vitro. The results indicated that both MCAO and OGD induced significant mitochondrial dysfunction in vivo and in vitro. The mitochondria became fragmented under hypoxia conditions, accompanied with upregulation of the heat shock protein 75 kDa glucose‑regulated protein (GRP75). Inhibition of GRP75 was able to effectively ameliorate mitochondrial calcium overload and preserve mitochondrial function, which may provide evidence for further translational studies of ischemic diseases.

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