Peroxiredoxin 6 delivery attenuates TNF-alpha-and glutamate-induced retinal ganglion cell death by limiting ROS levels and maintaining Ca2+ homeostasis.
Peroxiredoxin 6 delivery attenuates TNF-alpha-and glutamate-induced retinal ganglion cell death by limiting ROS levels and maintaining Ca2+ homeostasis.
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DOI：
10.1016/j.brainres.2008.07.076
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发表时间：
2008-10-03
期刊：
影响因子：
2.9
通讯作者：
Singh DP
中科院分区：
文献类型：
--
作者：
Fatma N;Kubo E;Sen M;Agarwal N;Thoreson WB;Camras CB;Singh DP
活性氧（ROS）的高表达与神经系统疾病有关。青光眼的一个主要事件是视网膜神经节细胞（RGC）的死亡，这与RGC局部微环境中谷氨酸和TNF-α水平升高有关。在此，我们表明，转导过氧化物酶6（PRDX 6）减弱TNFα和谷氨酸诱导的RGC死亡，通过限制ROS和维持Ca 2+稳态。大鼠视网膜的免疫组化染色揭示了PRDX 6在RGCs中的存在，Western和实时PCR分析揭示了PRDX 6蛋白和mRNA的丰度。用谷氨酸和/或TNF-α处理的RGCs显示ROS水平升高和PRDX 6表达降低，并发生凋亡。PRDX 6通过降低ROS水平和NF-kB活化，并限制细胞内Ca 2+内流增加，保护RGCs免受谷氨酸和TNF-α诱导的细胞毒性。结果提供了使用PRDX 6阻断青光眼和其他神经元疾病中ROS介导的病理生理学的基本原理。
Higher expression of reactive oxygen species (ROS) is implicated in neurological disorders. A major event in glaucoma, the death of retinal ganglion cells (RGCs), has been associated with elevated levels of glutamate and TNF-α in the RGCs’ local microenvironment. Herein we show that the transduction of Peroxiredoxin 6 (PRDX6) attenuates TNFα- and glutamate-induced RGC death, by limiting ROS and maintaining Ca2+ homeostasis. Immunohistochemical staining of rat retina disclosed the presence of PRDX6 in RGCs, and Western and real-time PCR analysis revealed an abundance of PRDX6 protein and mRNA. RGCs treated with glutamate and/or TNF-α displayed elevated levels of ROS and reduced expression of PRDX6, and underwent apoptosis. A supply of PRDX6 protected RGCs from glutamate and TNF-α induced cytotoxicity by reducing ROS level and NF-kB activation, and limiting increased intracellular Ca2+ influx. Results provide a rationale for use of PRDX6 for blocking ROS-mediated pathophysiology in glaucoma and other neuronal disorders.
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影响因子：
4.4
作者：
Charles, I;Khalyfa, A;Agarwal, N
通讯作者：
Agarwal, N
影响因子：
3.9
作者：
HALESTRAP, AP;GRIFFITHS, EJ;CONNERN, CP
通讯作者：
CONNERN, CP
影响因子：
4.8
作者：
DICKINSON, JL;BATES, EJ;ANTALIS, TM
通讯作者：
ANTALIS, TM
DOI：
10.1073/pnas.91.15.7017
发表时间：
1994-07-19
影响因子：
11.1
作者：
CHAE, HZ;ROBISON, K;RHEE, SG
通讯作者：
RHEE, SG
影响因子：
16.2
作者：
CHENG, B;CHRISTAKOS, S;MATTSON, MP
通讯作者：
MATTSON, MP