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	SERPINA3K Protects against Oxidative Stress via Modulating ROS Generation/Degradation and KEAP1-NRF2 Pathway in the Corneal Epithelium
	Zhou, Tong ; Zong, Rongrong ; Zhang, Zhoujing ; Zhu, Chengpeng ; Pan, Fangyu ; Xiao, Xinye ; Liu, Zhen ; He, Hui ; Ma, Jian-xing ; Liu, Zuguo ; Zhou, Yueping ; Zhou YP(周跃平) ; Zhou T(周彤) ; Ma JX(马建兴) ; Liu ZG(刘祖国)
	2012-07
关键词	ENDOTHELIAL-CELLS NADPH OXIDASES WNT PATHWAY ACTIVATION DYSTROPHY NRF2 PATHOPHYSIOLOGY MECHANISMS EXPRESSION PHYSIOLOGY
英文摘要	PURPOSE. We recently reported that SERPINA3K (SA3K), a member of the serine proteinase inhibitor (SERPIN) family, has antiangiogenic and anti-inflammatory activities. Here we investigated the antioxidant effects of SA3K in the corneal epithelium and the mechanism underlying its action. METHODS. We established the oxidative stress models induced by hydrogen peroxide (H2O2) in cultured human corneal epithelial (HCE) cells and in rat corneal epithelium in vivo. Cell viability, flow cytometry, and TUNEL analysis were conducted to detect viable cells and cell death; reactive oxygen species (ROS) and 3-Nitrotyrosine fluorescent assay was applied to measure ROS levels. Activity assay, immunostaining, Western blot, and quantitative RT-PCR were performed to analyze the factors of the ROS generation/degradation system and pathway. RESULTS. SA3K protected the HCE cells from H2O2-induced oxidative stress in a dose- and time-dependent manner. SA3K also significantly reduced the production of ROS. Regarding the mechanism underlying these effects, SA3K downregulated ROS generation by inhibiting NOX4 and upregulated ROS degradation by increasing the activity of superoxide dismutases and catalase. Furthermore, H2O2 induced activation of the Kelch-like ECH-associated protein 1 (KEAP1)/NF-E2-related factor-2 (NRF2) pathway, while SA3K inhibited H2O2-induced activation of KEAP1 and NRF2 and their downstream factors, including NAD(P)H quinone oxidoreductase and glutathione S-transferase. In the H2O2-induced rat corneal epithelium, SA3K alleviated the oxidative stress and downregulated NOX4 and NRF2. CONCLUSIONS. Collectively, SA3K protects against oxidative stress by targeting the ROS generation/degradation system and modulating the KEAP1-NRF2 signaling pathway. (Invest Ophthalmol Vis Sci. 2012;53:5033-5043) DOI: 10.1167/iovs.12-9729; Natural Science Foundation of China Grant [81170818]; Natural Science Foundation of Fujian Province of China Grant [2011J01255]
语种	英语
出版者	ASSOC RESEARCH VISION OPHTHALMOLOGY INC
内容类型	期刊论文
源URL	[http://dx.doi.org/10.1167/iovs.12-9729]
专题	医学院－已发表论文
推荐引用方式 GB/T 7714	Zhou, Tong,Zong, Rongrong,Zhang, Zhoujing,et al. SERPINA3K Protects against Oxidative Stress via Modulating ROS Generation/Degradation and KEAP1-NRF2 Pathway in the Corneal Epithelium[J],2012.
APA	Zhou, Tong.,Zong, Rongrong.,Zhang, Zhoujing.,Zhu, Chengpeng.,Pan, Fangyu.,...&刘祖国.(2012).SERPINA3K Protects against Oxidative Stress via Modulating ROS Generation/Degradation and KEAP1-NRF2 Pathway in the Corneal Epithelium..
MLA	Zhou, Tong,et al."SERPINA3K Protects against Oxidative Stress via Modulating ROS Generation/Degradation and KEAP1-NRF2 Pathway in the Corneal Epithelium".(2012).

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