N-Acetylcysteine Protects Against Hypoxia Mimetic-Induced Autophagy by Targeting the HIF-1α Pathway in Retinal Ganglion Cells

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• 作者：Lan Yang (1)
  Panpan Tan (1)
  Wei Zhou (1)
  Xu Zhu (1)
  Yongyao Cui (1)
  Liang Zhu (1)
  Xuemei Feng (1)
  Hong Qi (1)
  Jun Zheng (1)
  Ping Gu (2)
  Xianqun Fan (2)
  Hongzhuan Chen (1)
  
• 关键词：N ; acetylcysteine ; Hypoxia ; Autophagic cell death ; HIF ; 1α ; Retinal ganglion cells
• 刊名：Cellular and Molecular Neurobiology
• 出版年：2012
• 出版时间：November 2012
• 年：2012
• 卷：32
• 期：8
• 页码：1275-1285
• 全文大小：692KB
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• 作者单位：Lan Yang (1)
  Panpan Tan (1)
  Wei Zhou (1)
  Xu Zhu (1)
  Yongyao Cui (1)
  Liang Zhu (1)
  Xuemei Feng (1)
  Hong Qi (1)
  Jun Zheng (1)
  Ping Gu (2)
  Xianqun Fan (2)
  Hongzhuan Chen (1)
  
  1. Department of Pharmacology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai, 200025, China
  2. Department of Ophthalmology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhi Zao Ju Road, Shanghai, 200011, China
  
• ISSN：1573-6830

文摘

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 of N-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 CoCl2 exposure, 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.