Neuroserpin Attenuates H₂O₂-Induced Oxidative Stress in Hippocampal Neurons via AKT and BCL-2 Signaling Pathways

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• 作者：Yong Cheng ; Y. Peng Loh ; Nigel P. Birch
• 关键词：Oxidative stress ; Reactive oxygen species ; Protease inhibitor ; Neuroprotection ; Hippocampal neurons
• 刊名：Journal of Molecular Neuroscience
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：61
• 期：1
• 页码：123-131
• 全文大小：
• 刊物主题：Neurosciences; Neurochemistry; Cell Biology; Proteomics; Neurology;
• 出版者：Springer US
• ISSN：1559-1166
• 卷排序：61

文摘

Oxidative stress plays a critical role in neuronal injury and is associated with various neurological diseases. Here, we explored the potential protective effect of neuroserpin against oxidative stress in primary cultured hippocampal neurons. Our results show that neuroserpin inhibits H₂O₂-induced neurotoxicity in hippocampal cultures as measured by WST, LDH release, and TUNEL assays. We found that neuroserpin enhanced the activation of AKT in cultures subjected to oxidative stress and that the AKT inhibitor Ly294002 blocked this neuroprotective effect. Neuroserpin increased the expression of the anti-apoptotic protein BCL-2 and blocked the activation of caspase-3. Neuroserpin did not increase the level of neuroprotection over levels seen in neurons transduced with a BCL-2 expression vector, and an inhibitor of Trk receptors, K252a, did not block neuroserpin’s effect. Taken together, our study demonstrates that neuroserpin protects against oxidative stress-induced dysfunction and death of primary cultured hippocampal neurons through the AKT-BCL-2 signaling pathway through a mechanism that does not involve the Trk receptors and leads to inhibition of caspase-3 activation.