GRP78 suppresses lipid peroxidation and promotes cellular antioxidant levels in glial cells following hydrogen peroxide exposure.

GRP78 suppresses lipid peroxidation and promotes cellular antioxidant levels in glial cells following hydrogen peroxide exposure.
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DOI:
10.1371/journal.pone.0086951
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Mochida J
Mochida J
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Suyama K;Watanabe M;Sakabe K;Otomo A;Okada Y;Terayama H;Imai T;Mochida J

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氧化应激由活性氧(ROS)的过度产生引起,已被证明有助于与神经创伤和神经退行性疾病相关的细胞损伤。ROS通过脂质、蛋白质和DNA的直接氧化或作为信号分子触发细胞凋亡途径介导细胞损伤。78 kDa葡萄糖调节蛋白(GRP78)是一种内质网伴侣,被认为可以保护细胞免受ros诱导的损伤。然而,GRP78的保护机制尚不清楚。在本研究中,我们使用短暂过表达GRP78的C6胶质瘤细胞来研究GRP78对氧化应激(过氧化氢)诱导的损伤的保护作用。我们的研究结果表明,与非GRP78过表达的细胞相比,GRP78过表达的细胞可显著保护细胞免受ros诱导的细胞损伤,这很可能是由于GRP78过表达的细胞具有更高水平的谷胱甘肽(GSH)和NAD(P)H:醌氧化还原酶1 (NQO1),这两种抗氧化剂可保护细胞免受氧化应激。虽然过氧化氢处理在非grp78过表达细胞中增加了脂质过氧化,但在grp78过表达细胞中这种增加明显减少。综上所述,这些结果表明GRP78通过调节GSH和NQO1的表达,在保护胶质细胞抗氧化应激中发挥重要作用。
Oxidative stress, caused by the over production of reactive oxygen species (ROS), has been shown to contribute to cell damage associated with neurotrauma and neurodegenerative diseases. ROS mediates cell damage either through direct oxidation of lipids, proteins and DNA or by acting as signaling molecules to trigger cellular apoptotic pathways. The 78 kDa glucose-regulated protein (GRP78) is an ER chaperone that has been suggested to protect cells against ROS-induced damage. However, the protective mechanism of GRP78 remains unclear. In this study, we used C6 glioma cells transiently overexpressing GRP78 to investigate the protective effect of GRP78 against oxidative stress (hydrogen peroxide)-induced injury. Our results showed that the overexpression of GRP78 significantly protected cells from ROS-induced cell damage when compared to non-GRP78 overexpressing cells, which was most likely due to GRP78-overexpressing cells having higher levels of glutathione (GSH) and NAD(P)H:quinone oxidoreductase 1 (NQO1), two antioxidants that protect cells against oxidative stress. Although hydrogen peroxide treatment increased lipid peroxidation in non-GRP78 overexpressing cells, this increase was significantly reduced in GRP78-overexpressing cells. Overall, these results indicate that GRP78 plays an important role in protecting glial cells against oxidative stress via regulating the expression of GSH and NQO1.
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