Neuroprotective effect of peroxiredoxin 6 against hypoxia-induced retinal ganglion cell damage.
Neuroprotective effect of peroxiredoxin 6 against hypoxia-induced retinal ganglion cell damage.
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DOI：
10.1186/1471-2202-11-125
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发表时间：
2010-10-05
期刊：
影响因子：
2.4
通讯作者：
Singh DP
中科院分区：
文献类型：
--
作者：
Tulsawani R;Kelly LS;Fatma N;Chhunchha B;Kubo E;Kumar A;Singh DP
对细胞外环境变化的反应能力是细胞存活的先决条件。细胞对环境的反应包括提升防御系统，如抗氧化防御系统。缺氧诱发的活性氧（ROS）驱动的氧化应激是导致致盲性疾病的视网膜神经节细胞（RGC）死亡的潜在机制。蛋白质过氧化物氧还蛋白6（PRDX 6）在响应于应激物的负调节死亡信号传导中起多效性作用，从而稳定细胞内稳态。我们已经表明，暴露于缺氧（1%）或缺氧模拟氯化钴的RGCs显示PRDX 6表达减少，ROS表达增加，NF-κB活化。这些细胞经历凋亡，而PRDX 6过表达的细胞表现出对缺氧驱动的RGC死亡的抗性。将RGCs暴露于含1%氧气或氯化钴（0-400 μM）的缺氧条件下，暴露48和72 h后，显示约30%-70%的凋亡细胞死亡。Western分析和实时定量PCR显示，PRDX 6在缺氧24 h表达升高，而PRDX 6蛋白和mRNA表达从缺氧暴露后48 h开始下降。与此同时，RGC显示ROS表达增加，NF-κB活化，Ik B磷酸化/降解，如H2 DCF-DA和反式激活试验所示。这些缺氧诱导的不良反应可以通过PRDX 6的过表达来逆转。由于细胞中丰富的PRDX 6能够减弱缺氧诱导的RGC死亡，因此该蛋白可能被开发为一种新型治疗剂，用于延缓RGC损伤并延迟青光眼和其他由增加的ROS产生的与缺氧相关的死亡信号传导引起的疾病的进展。
The ability to respond to changes in the extra-intracellular environment is prerequisite for cell survival. Cellular responses to the environment include elevating defense systems, such as the antioxidant defense system. Hypoxia-evoked reactive oxygen species (ROS)-driven oxidative stress is an underlying mechanism of retinal ganglion cell (RGC) death that leads to blinding disorders. The protein peroxiredoxin 6 (PRDX6) plays a pleiotropic role in negatively regulating death signaling in response to stressors, and thereby stabilizes cellular homeostasis. We have shown that RGCs exposed to hypoxia (1%) or hypoxia mimetic cobalt chloride display reduced expression of PRDX6 with higher ROS expression and activation of NF-κB. These cells undergo apoptosis, while cells with over-expression of PRDX6 demonstrate resistance against hypoxia-driven RGC death. The RGCs exposed to hypoxia either with 1% oxygen or cobalt chloride (0-400 μM), revealed ~30%-70% apoptotic cell death after 48 and 72 h of exposure. Western analysis and real-time PCR showed elevated expression of PRDX6 during hypoxia at 24 h, while PRDX6 protein and mRNA expression declined from 48 h onwards following hypoxia exposure. Concomitant with this, RGCs showed increased ROS expression and activation of NF-κB with IkB phosphorylation/degradation, as examined with H2DCF-DA and transactivation assays. These hypoxia-induced adverse reactions could be reversed by over-expression of PRDX6. Because an abundance of PRDX6 in cells was able to attenuate hypoxia-induced RGC death, the protein could possibly be developed as a novel therapeutic agent acting to postpone RGC injury and delay the progression of glaucoma and other disorders caused by the increased-ROS-generated death signaling related to hypoxia.
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影响因子：
29.4
作者：
Cummins, Eoin P.;Seeballuck, Fergal;Taylor, Cormac T.
通讯作者：
Taylor, Cormac T.
影响因子：
4.4
作者：
Charles, I;Khalyfa, A;Agarwal, N
通讯作者：
Agarwal, N
鉴定过氧蛋白6在乳腺癌进展中的功能作用。
DOI：
10.1186/bcr1789
发表时间：
2007
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Chang XZ;Li DQ;Hou YF;Wu J;Lu JS;Di GH;Jin W;Ou ZL;Shen ZZ;Shao ZM
通讯作者：
Shao ZM
影响因子：
5.3
作者：
Bell, Eric L.;Klimova, Tatyana A.;Chandel, Navdeep S.
通讯作者：
Chandel, Navdeep S.
影响因子：
2.9
作者：
Fatma N;Kubo E;Sen M;Agarwal N;Thoreson WB;Camras CB;Singh DP
通讯作者：
Singh DP