Autotaxin protects microglial cells against oxidative stress
Autotaxin protects microglial cells against oxidative stress
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DOI：
10.1016/j.freeradbiomed.2011.11.014
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发表时间：
2012-01-15
影响因子：
7.4
通讯作者：
Bourdon, Emmanuel
中科院分区：
文献类型：
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作者：
Awada, Rana;Rondeau, Philippe;Bourdon, Emmanuel
当抗氧化剂防御被氧反应物质淹没时，氧化应激就会发生，并可能导致细胞损伤，如在几种神经退行性疾病中所见。小胶质细胞是中枢神经系统中的特化细胞，其在对病理事件的反应中充当主动免疫防御的第一和主要形式。自分泌运动因子（ATX）通过其酶促产生溶血磷脂酸（LPA）在关键细胞功能的调节中起重要作用。在这项研究中，我们研究了ATX在小胶质细胞对氧化应激反应中的潜在作用。我们表明，用过氧化氢（H2O2）处理小胶质细胞BV2细胞系刺激ATX表达和LPA产生。ATX的稳定过表达可抑制小胶质细胞活化（CD11b表达）并保护免受H2O2处理诱导的细胞损伤。在LPA受体拮抗剂Ki 16425存在下，ATX的这种保护作用部分降低。ATX过表达还与细胞内ROS形成、羰基化蛋白积累、蛋白酶体活性和过氧化氢酶表达的减少相关。我们的研究结果表明，上调ATX表达的小胶质细胞可能是一种机制，保护免受氧化应激，从而减少神经系统的炎症。(C)2011 Elsevier Inc. All rights reserved.
Oxidative stress occurs when antioxidant defenses are overwhelmed by oxygen-reactive species and can lead to cellular damage, as seen in several neurodegenerative disorders. Microglia are specialized cells in the central nervous system that act as the first and main form of active immune defense in the response to pathological events. Autotaxin (ATX) plays an important role in the modulation of critical cellular functions, through its enzymatic production of lysophosphatidic acid (LPA). In this study, we investigated the potential role of ATX in the response of microglial cells to oxidative stress. We show that treatment of a microglial BV2 cell line with hydrogen peroxide (H2O2) stimulates ATX expression and LPA production. Stable overexpression of ATX inhibits microglial activation (CD11b expression) and protects against H2O2-treatment-induced cellular damage. This protective effect of ATX was partially reduced in the presence of the LPA-receptor antagonist Ki16425. ATX overexpression was also associated with a reduction in intracellular ROS formation, carbonylated protein accumulation, proteasomal activity, and catalase expression. Our results suggest that upregulation of ATX expression in microglia could be a mechanism for protection against oxidative stress, thereby reducing inflammation in the nervous system. (C) 2011 Elsevier Inc. All rights reserved.