Induction of thioredoxin reductase as an adaptive response to acrolein in human umbilical vein endothelial cells
Induction of thioredoxin reductase as an adaptive response to acrolein in human umbilical vein endothelial cells
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DOI：
10.1016/j.bbrc.2004.12.104
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发表时间：
2005-02-25
影响因子：
3.1
通讯作者：
Taniguchi, N
中科院分区：
文献类型：
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作者：
Park, YS;Misonou, Y;Taniguchi, N
丙烯醛是一种高度亲电的α-β-不饱和醛，人类在各种环境条件下都会接触到它，也是脂质过氧化的产物。不饱和醛水平的升高和抗氧化状态的降低在许多人类疾病的发病机制中起着重要作用，如阿尔茨海默氏症、动脉粥样硬化和糖尿病。哺乳动物硫氧还蛋白还原酶是一种催化氧化的硫氧还蛋白还原的硒蛋白，是一种中枢抗氧化酶。这里报道的研究结果表明，无论是在体外还是在体内，低浓度的丙烯醛都能迅速灭活tr。这些数据表明，丙烯醛可能直接使TR失活，导致细胞氧化损伤增加。此外，我们还发现，丙烯醛最初使人脐静脉内皮细胞(HUVEC)中的TR分子失活，触发了一种诱导人脐静脉内皮细胞(HUVEC)表达TR基因的代偿信号。本研究结果提示HUVEC可能通过上调TR值来保护细胞免受丙烯醛的损伤，这是对氧化应激的一种适应性反应。(C)2004 Elsevier Inc.保留所有权利。
Acrolein is a highly electrophilic alpha,beta-unsaturated aldehyde to which humans are exposed in a variety of environment situations and is also a product of lipid peroxidation. Increased unsaturated aldehyde levels and reduced antioxidant status play an important role in the pathogenesis of a number of human diseases such as Alzheimer's, atherosclerosis, and diabetes. Mammalian thioredoxin reductase (TR), a central antioxidant enzyme, is a selenoprotein that catalyzes the reduction of oxidized thioredoxin. The findings reported here show that low concentrations of acrolein rapidly inactivate TR, both in vitro and in vivo. These data suggest that acrolein may directly inactivate TR, resulting in an increase in oxidative cellular damage. In addition, we also found that the initial inactivation of TR molecules by acrolein triggers a compensatory signal for inducing TR gene expression in human umbilical vein endothelial cells (HUVEC). The results of the present study suggest that HUVEC may have a protective system against cell damage by acrolein via the upregulation of TR, which is an adaptive response to oxidative stress. (C) 2004 Elsevier Inc. All rights reserved.