Transmembrane p24 trafficking protein 10 (TMED10) inhibits mitochondrial damage and protects neurons in ischemic stroke via the c-Jun N-terminal kinase (JNK) signaling pathway
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- Li Qiushi
- Medical College of Soochow University, No. 1, Shizi Street, Suzhou, Jiangsu Province, 215021, P.R. China Department of Neurology, The First Affiliated Hospital of Jinzhou Medical University, No. 2, Section 5, Renmin Street, Jinzhou, Liaoning Province, 121000, P.R. China
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- Liu Xuying
- Department of Neurology, The Third Affiliated Hospital of Jinzhou Medical University, No. 2, Section 5, Heping Road, Linghe District, Jinzhou, Liaoning Province, 121000, P.R. China
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- Xing Ruixian
- Department of Neurology, The First Affiliated Hospital of Jinzhou Medical University, No. 2, Section 5, Renmin Street, Jinzhou, Liaoning Province, 121000, P.R. China
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- Sui Rubo
- Medical College of Soochow University, No. 1, Shizi Street, Suzhou, Jiangsu Province, 215021, P.R. China Department of Neurology, The First Affiliated Hospital of Jinzhou Medical University, No. 2, Section 5, Renmin Street, Jinzhou, Liaoning Province, 121000, P.R. China
抄録
<p> Stroke, a type of acute cerebrovascular disease, is a global disease with high mortality. Neuronal ischemia and hypoxia are closely related to occurrence and development of cognitive impairment. Transmembrane p24 trafficking protein 10 (TMED10) as a transmembrane protein involves in vesicle protein transport in the secretory pathways. However, the function and mechanism of TMED10 on ischemic stroke and cognitive impairments remain unclear. In current study, TMED10 was highly expressed in cerebral ischemic penumbra of middle cerebral artery occlusion (MCAO) mouse model. Downregulation of TMED10 suppressed cell survival and facilitated apoptosis in primary cortical neurons, which were grown under oxygen glucose deprivation/reoxygenation (OGD/R) condition. Upregulation of TMED10 protected neurons form apoptosis induced by OGD/R. Further research indicated that the decrease of TMED10 resulted in neuronal mitochondrial injury through increasing reactive oxygen species (ROS) production. Meanwhile, TMED10 reduction induced neuronal apoptosis and mitochondrial damage through activating the c-Jun N-terminal kinase (JNK) pathway. Moreover, the knockdown of TMED10 increased cerebral infarction area, aggravated neuronal injury and promoted neuronal apoptosis through activating the JNK pathway in the cerebral ischemic penumbra of MCAO mouse model. Additionally, Morris water maze test verified that the severity of cognitive impairment increased with the decline of TMED10. Collectively, this study reveals that TMED10 inhibits mitochondrial damage, and protects neurons from apoptosis in MCAO-induced ischemic stroke and cognitive impairment via blocking the JNK pathway.</p>
収録刊行物
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- Experimental Animals
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Experimental Animals 72 (2), 151-163, 2023
公益社団法人 日本実験動物学会