S-Glutathionylation of Keap1: a new role for glutathione S-transferase pi in neuronal protection
S-Glutathionylation of Keap1: a new role for glutathione S-transferase pi in neuronal protection
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DOI：
10.1002/1873-3468.12177
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发表时间：
2016-05-01
期刊：
影响因子：
3.5
通讯作者：
Gama, Maria Joao
中科院分区：
文献类型：
--
作者：
Carvalho, Andreia Neves;Marques, Carla;Gama, Maria Joao
氧化应激是帕金森病（PD）的一个重要病理特征。谷胱甘肽S-转移酶pi（GSTP）是一种神经保护性抗氧化酶，在转录水平上由抗氧化主调节因子核因子-红细胞2相关因子2（Nrf 2）调节。在这里，我们第一次表明，MPTP诱导的氧化应激，GSTP增强S-谷胱甘肽的Kelch样ECH相关蛋白1（Keap 1），一个内源性阻遏物NRF 2，在体内。Keap 1的S-谷胱甘肽化导致Nrf 2激活，随后增加GSTP的表达。这种正反馈调节回路代表了GSTP增强大脑抗氧化保护的新机制。
Oxidative stress is a key pathological feature of Parkinson's disease (PD). Glutathione S-transferase pi (GSTP) is a neuroprotective antioxidant enzyme regulated at the transcriptional level by the antioxidant master regulator nuclear factor-erythroid 2-related factor 2 (Nrf2). Here, we show for the first time that upon MPTP-induced oxidative stress, GSTP potentiates S-glutathionylation of Kelch-like ECH-associated protein 1 (Keap1), an endogenous repressor of Nrf2, in vivo. S-glutathionylation of Keap1 leads to Nrf2 activation and subsequently increases expression of GSTP. This positive feedback regulatory loop represents a novel mechanism by which GSTP elicits antioxidant protection in the brain.