Tat-HSP22 inhibits oxidative stress-induced hippocampal neuronal cell death by regulation of the mitochondrial pathway

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• 作者：Hyo Sang Jo ; Dae Won Kim ; Min Jea Shin ; Su Bin Cho ; Jung Hwan Park…
• 关键词：Tat ; HSP22 ; Oxidative stress ; Apoptosis ; Ischemia ; Protein therapy
• 刊名：Molecular Brain
• 出版年：2017
• 出版时间：December 2017
• 年：2017
• 卷：10
• 期：1
• 全文大小：7605KB
• 刊物主题：Neurosciences; Neurology; Psychopharmacology;
• 出版者：BioMed Central
• ISSN：1756-6606
• 卷排序：10

文摘

Oxidative stress plays an important role in the progression of various neuronal diseases including ischemia. Heat shock protein 22 (HSP22) is known to protect cells against oxidative stress. However, the protective effects and mechanisms of HSP22 in hippocampal neuronal cells under oxidative stress remain unknown. In this study, we determined whether HSP22 protects against hydrogen peroxide (H₂O₂)-induced oxidative stress in HT-22 using Tat-HSP22 fusion protein. We found that Tat-HSP22 transduced into HT-22 cells and that H₂O₂-induced cell death, oxidative stress, and DNA damage were significantly reduced by Tat-HSP22. In addition, Tat-HSP22 markedly inhibited H₂O₂-induced mitochondrial membrane potential, cytochrome c release, cleaved caspase-3, and Bax expression levels, while Bcl-2 expression levels were increased in HT-22 cells. Further, we showed that Tat-HSP22 transduced into animal brain and inhibited cleaved-caspase-3 expression levels as well as significantly inhibited hippocampal neuronal cell death in the CA1 region of animals in the ischemic animal model. In the present study, we demonstrated that transduced Tat-HSP22 attenuates oxidative stress-induced hippocampal neuronal cell death through the mitochondrial signaling pathway and plays a crucial role in inhibiting neuronal cell death, suggesting that Tat-HSP22 protein may be used to prevent oxidative stress-related brain diseases including ischemia.