Oxidative stress and DNA damage induced by cadmium in the human keratinocyte HaCaT cell line:: Role of glutathione in the resistance to cadmium
Oxidative stress and DNA damage induced by cadmium in the human keratinocyte HaCaT cell line:: Role of glutathione in the resistance to cadmium
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DOI：
10.1016/j.tox.2007.10.005
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发表时间：
2008-01-14
期刊：
影响因子：
4.5
通讯作者：
Guiraud, Pascale
中科院分区：
文献类型：
--
作者：
Nzengue, Yves;Steiman, Regine;Guiraud, Pascale
镉通过与其他金属的相互作用和氧化应激诱导等复杂的机制影响细胞的动态平衡并产生损害。本工作以人角质形成细胞系(HaCaT)为模型，研究了镉对细胞大分子的氧化损伤、对抗氧化系统的影响以及谷胱甘肽在细胞对镉毒性保护中的作用。细胞分别与镉(3、15、50和100mM)孵育24和48h。高剂量镉诱导细胞毒性：100mU/M镉24小时后死亡率为30%，48小时后死亡率为50%。通过硫代巴比妥酸反应物测定、硫代巴比妥酸测定和彗星试验，分别观察了镉对脂质和蛋白质的氧化及DNA损伤。细胞毒作用与细胞内镉含量密切相关。镉处理降低了谷胱甘肽过氧化物酶和过氧化氢酶活性，提高了谷胱甘肽还原酶活性和谷胱甘肽浓度。超氧化物歧化酶活性无明显变化。镉暴露前谷胱甘肽的耗尽增加了细胞毒效应，并引发了DNA损伤。我们的结果表明，羟基自由基可能是镉引起的氧化应激的主要参与物质，谷胱甘肽可能在保护HaCaT细胞免受细胞毒性方面发挥主要作用，但主要是在镉诱导的DNA损伤中发挥作用。(C)2007爱思唯尔爱尔兰有限公司。保留所有权利。
Cadmium affects the cellular homeostasis and generates damage via complex mechanisms involving interactions with other metals and oxidative stress induction. In this work we used a human keratinocyte cell line (HaCaT) as a model to study the oxidative damage induced by cadmium to cellular macromolecules, its effect on the antioxidant systems and the role of glutathione in cell protection toward cadmium toxicity. The cells were incubated for 24 and 48 h with cadmium (3, 15, 50 and 100 mu M). High doses of cadmium were required to induce a cytotoxicity: 100 mu M lead to 30% mortality after 24 It and 50% after 48 h. The oxidation of lipids and proteins and the DNA damage, respectively, assessed by thiobarbituric acid reactants determination, thiol group measurement and comet assay, were observed for 50-100 mu M cadmium. The cytotoxic effects were strongly correlated to the cellular cadmium content. The glutathione peroxidase and the catalase activities were decreased, while the glutathione reductase activity and the glutathione concentration were increased after cadmium treatment. The superoxide dismutases activities were unchanged. A depletion in glutathione prior to cadmium exposure increased the cytotoxic effects and provoked DNA damage. Our results suggested that the hydroxyl radical could be the major compound involved in the oxidative stress generated by cadmium and that glutathione could play a major role in the protection of HaCaT cells from cytotoxicity but mostly from DNA damage induced by cadmium. (c) 2007 Elsevier Ireland Ltd. All rights reserved.