Effect of oxidative stress on UDP-glucuronosyltransferases in rat astrocytes
Effect of oxidative stress on UDP-glucuronosyltransferases in rat astrocytes
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DOI：
10.1016/j.toxlet.2012.07.014
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发表时间：
2012-09-18
影响因子：
3.5
通讯作者：
Heydel, Jean-Marie
中科院分区：
文献类型：
--
作者：
Gradinaru, Daniela;Minn, Anne-Laure;Heydel, Jean-Marie
目前的工作报告了有关诱导氧化应激对大脑中 UDP-葡萄糖醛酸基转移酶 (UGT) 主要表达亚型的影响的数据。将大鼠培养的星形胶质细胞暴露于氧化还原循环外源化合物（如醌和联吡啶鎓离子）48 小时后，分析 UGT1A6 和 UGT1A7 的表达以及针对 1-萘酚的酶活性。还研究了 NADPH：细胞色素 P450 还原酶和 NAD(P) H：醌氧化还原酶 1 (NQO1) 的表达。氧化应激导致星形胶质细胞形态发生显着有害变化，降低细胞活力，并由于蛋白质氧化而抑制 UGT 的催化功能。或者，在幸存的受损星形胶质细胞中，氧化条件诱导了异生物质解毒酶的显着过度活性和过度表达，作为适应性反应。褪黑激素的存在显着阻止了这些作用，表明其对活性氧的直接抗氧化作用，进一步反映了 UGT1A6 和 UGT1A7 的葡萄糖醛酸化活性和转录调节。结果表明，UGTs的催化特性以及大鼠星形胶质细胞中UGT1A6、UGT1A7、NQO1和NADPH：细胞色素P450还原酶的表达均受促氧化环境的影响很大。总之，氧化细胞状态的实验性增加可能对解毒酶系统的活性和表达产生直接和长期的影响。 (c) 2012 Elsevier Ireland Ltd. 保留所有权利。
The present work reports data regarding effects of an induced oxidative stress on the mainly expressed isoforms of UDP-glucuronosyltransferases (UGTs) in the brain. UGT1A6 and UGT1A7 expression and enzymatic activities toward the 1-naphthol were analyzed in rat cultured astrocytes following the exposure for 48 h to redox-cycling xenobiotic compounds such as quinones and bipyridinium ions. The expression of NADPH: cytochrome P450 reductase and NAD(P) H: quinone oxidoreductase 1 (NQO1) was also investigated. Oxidative stress induced significant deleterious changes in astrocyte morphology, decreased cell viability and inhibited catalytic function of UGTs as a result of protein oxidation. Alternatively, in the surviving impaired astrocytes, oxidative conditions induced a significant overactivity and overexpression of xenobiotic detoxification enzymes, as adaptive response. These effects were significantly prevented by the presence of melatonin, suggesting its direct antioxidant action on reactive oxygen species, reflected further on the glucuronidation activity and transcriptional regulation of both UGT1A6 and UGT1A7. Results show that both catalytic properties of UGTs and the expression of UGT1A6, UGT1A7, NQO1 and NADPH: cytochrome P450 reductase in rat astrocytes are greatly influenced by the pro- oxidative environment. In conclusion, an experimental increase in oxidative cellular status could have both immediate and long term consequences on detoxification enzymatic system activity and expression. (c) 2012 Elsevier Ireland Ltd. All rights reserved.