Induction of Thioredoxin Reductase Gene Expression by Peroxynitrite in Human Umbilical Vein Endothelial Cells
Induction of Thioredoxin Reductase Gene Expression by Peroxynitrite in Human Umbilical Vein Endothelial Cells
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过氧亚硝酸盐诱导人脐静脉内皮细胞硫氧还蛋白还原酶基因表达
DOI：
10.1515/bc.2002.070
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发表时间：
2002
期刊：
影响因子：
--
通讯作者：
Naoyuki Taniguchi
中科院分区：
文献类型：
--
作者：
Y. Park;N. Fujiwara;Y. Koh;Y. Miyamoto;Keiichiro Suzuki;K. Honke;Naoyuki Taniguchi
摘要 硫氧还蛋白还原酶（TR）是一种黄素蛋白，以NADPH依赖性方式催化氧化硫氧还蛋白的还原，并且在C末端附近含有硒代半胱氨酸残基。 TR 在防止氧化应激以及调节细胞生长和细胞死亡方面发挥着重要作用。已在哺乳动物体内的多种细胞类型中观察到组成型 TR 表达，包括内皮细胞。后者持续暴露于外源性和内源性一氧化氮 (NO) 和 NO 衍生物质。活性氮（RNS）与病理事件相关，导致细胞和组织损伤，并伴有炎症、动脉粥样硬化和自身免疫性疾病。在这项研究中，我们报告了过氧亚硝酸盐对人脐静脉内皮细胞 (HUVEC) TR 的影响。暴露于过氧亚硝酸盐供体 SIN-1 1 小时导致 TR 活性下降。有趣的是，活性在24小时内完全恢复。为了进一步研究这一机制，我们在 mRNA 和蛋白质水平上检测了 TR 的表达。 SIN-1处理后6小时内TR mRNA水平显着升高，HUVECs中TR蛋白水平也升高。这些结果表明过氧亚硝酸盐对TR的失活可能与HUVEC中TR基因的上调有关。因此，HUVEC 具有独特的保护机制，可以通过 TR 诱导维持细胞内氧化还原状态的平衡，作为对硝基氧化应激的适应性反应。
Abstract Thioredoxin reductase (TR), a flavoprotein, catalyzes the reduction of oxidized thioredoxin in a NADPHdependent manner, and contains a selenocysteine residue near the Cterminus. TR plays an important role in protecting against oxidative stress and in regulating cell growth and cell death. Constitutive TR expression has been observed in several cell types of the mammalian body, including endothelial cells. The latter are continually exposed to both exogenous and endogenous sources of nitric oxide (NO) and NOderived species. Reactive nitrogen species (RNS) are associated with pathological events, contributing to the cell and tissue damage accompanying inflammation, atherogenesis and autoimmune diseases. In this study, we report on the effect of peroxynitrite on TR in human umbilical vein endothelial cells (HUVECs). Exposure to the peroxynitrite donor SIN-1 for 1 h resulted in a decrease in TR activity. Interestingly, the activity was completely restored within 24 h. To further examine this mechanism, the expression of TR at the mRNA and protein level was examined. TR mRNA levels were markedly increased by treatment of SIN-1 within 6 h, and TR protein level was also increased after the treatment in HUVECs. These results suggest that the inactivation of TR by peroxynitrite might be involved in the upregulation of the TR gene in HUVECs. Therefore, HUVECs have a unique protective mechanism that allows the maintenance of balance in intracellular redox status via TR induction as an adaptive response to nitrooxidative stress.
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DOI：
10.1073/pnas.91.15.7017
发表时间：
1994-07-19
影响因子：
11.1
作者：
CHAE, HZ;ROBISON, K;RHEE, SG
通讯作者：
RHEE, SG
影响因子：
3.9
作者：
ISCHIROPOULOS, H;ZHU, L;BECKMAN, JS
通讯作者：
BECKMAN, JS
自然杀伤增强因子 B 抗氧化特性的表征及其过氧化氢诱导表达。
DOI：
10.1006/taap.1997.8270
发表时间：
1997
期刊：
Toxicology and applied pharmacology.
影响因子：
--
作者：
Kim,AT;Sarafian,TA;Shau,H
通讯作者：
Shau,H
影响因子：
3.9
作者：
VANDERVLIET, A;EISERICH, JP;CROSS, CE
通讯作者：
CROSS, CE
DOI：
10.1515/bchm3.1994.375.2.81
发表时间：
1994-02-01
期刊：
BIOLOGICAL CHEMISTRY HOPPE-SEYLER
影响因子：
--
作者：
BECKMANN, JS;YE, YZ;BECKMAN, JS
通讯作者：
BECKMAN, JS