N-Acetylcysteine Protects Against Hypoxia Mimetic-Induced Autophagy by Targeting the HIF-1α Pathway in Retinal Ganglion Cells
N-Acetylcysteine Protects Against Hypoxia Mimetic-Induced Autophagy by Targeting the HIF-1α Pathway in Retinal Ganglion Cells
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DOI：
10.1007/s10571-012-9852-0
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发表时间：
2012-05
影响因子：
4
通讯作者：
Lan Yang;Panpan Tan;W. Zhou;Xu Zhu;Yong-yao Cui;Liang Zhu;Xue-mei Feng;H. Qi;Jun Zheng
中科院分区：
文献类型：
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作者：
Lan Yang;Panpan Tan;W. Zhou;Xu Zhu;Yong-yao Cui;Liang Zhu;Xue-mei Feng;H. Qi;Jun Zheng
Hypoxia-induced retinal ganglion cell (RGC) death has been proposed to be the critical event in the pathophysiology of glaucoma. Therefore, delaying or halting RGC degeneration, known as neuroprotection, is a novel and promising approach with potential clinical applications for treating glaucoma. In this study, we investigate hypoxia-induced cell death of RGCs and the underlying mechanisms ofN-acetylcysteine (NAC) as a neuroprotectant. To establish a model for chemical hypoxia-induced cell death, RGC-5 cells were treated with the hypoxia mimetic cobalt chloride (CoCl2). Following CoCl2exposure, significant levels of apoptotic and autophagic cell death were observed in RGC-5 cells, evidenced by lysosome dysfunction and autophagosome formation. Pretreating RGC-5 cells with NAC significantly counteracted the autophagic cell death. NAC-mediated neuroprotection was attributed to the direct scavenging of reactive oxygen species and was mediated by targeting the hypoxia-inducible factor-1α pathway via the BNIP3 and PI3K/Akt/mTOR pathways. These results provide insights into the degeneration of RGCs and present a potential clinical application for NAC as a neuroprotectant.
