CADMIUM RESISTANCE IN A549 CELLS CORRELATES WITH ELEVATED GLUTATHIONE CONTENT BUT NOT ANTIOXIDANT ENZYMATIC-ACTIVITIES
CADMIUM RESISTANCE IN A549 CELLS CORRELATES WITH ELEVATED GLUTATHIONE CONTENT BUT NOT ANTIOXIDANT ENZYMATIC-ACTIVITIES
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DOI：
10.1016/0891-5849(95)00099-j
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发表时间：
1995-12-01
影响因子：
7.4
通讯作者：
KANG, YJ
中科院分区：
文献类型：
--
作者：
HATCHER, EL;CHEN, Y;KANG, YJ
谷氨酰胺在镉毒性的细胞保护中起作用。谷胱甘肽发挥这一作用的机制尚未得到很好的理解。由于谷胱甘肽是一种重要的抗氧化剂，一些研究表明，镉诱导氧化应激，本研究进行，以确定是否镉抗性的发展与增强的抗氧化活性。人肺癌A549细胞的耐镉亚群，这是通过反复暴露于逐步增加的镉浓度的细胞开发的，进行了比较，镉敏感的。获得性镉抗性既不是由于镉吸收减少，也不是由于细胞金属硫蛋白合成增加。然而，谷氨酸含量显着升高，在镉抗性细胞。与此相反，谷胱甘肽氧化还原循环相关的酶，谷胱甘肽过氧化物酶和还原酶的活动，是不变的。另外两种抗氧化酶，超氧化物歧化酶和过氧化氢酶，也没有改变。结果表明，镉抗性在A549细胞的发展不太可能从增强抗氧化酶活性的结果，虽然它是与细胞谷胱甘肽水平升高。此外，γ-谷氨酰半胱氨酸合成酶（谷胱甘肽生物合成的限速酶）的mRNA和DNA水平的测量显示，该酶的表达增强而非基因扩增可能是细胞谷胱甘肽水平升高的原因。
Glutathione has been implicated to function in cytoprotection against cadmium toxicity. The mechanism by which glutathione plays this role has not been well understood. Because glutathione is an important antioxidant and several studies have shown that cadmium induces oxidative stress, this study was undertaken to determine whether development of cadmium resistance is linked to enhanced antioxidant activities. A cadmium-resistant subpopulation of human lung carcinoma A549 cells, which was developed by repeatedly exposing the cells to step-wise increased cadmium concentrations, was compared to a cadmium-sensitive one. The acquired cadmium resistance resulted from neither decreased cadmium uptake nor enhanced cellular metallothionein synthesis. Glutathione content, however, was markedly elevated in the cadmium-resistant cells. In contrast, the activities of the glutathione redox cycle related enzymes, glutathione peroxidase and reductase, were unchanged. Two other antioxidant enzymes, superoxide dismutase and catalase, were also not altered. The results suggest that the development of cadmium resistance in A549 cells unlikely results from enhanced antioxidant enzyme activities, although it is associated with elevated cellular glutathione levels. In addition, measurement of the mRNA and DNA levels for gamma-glutamylcysteine synthetase, the rate-limiting enzyme for glutathione biosynthesis, revealed that, enhanced expression of the enzyme but not gene amplification is likely responsible for the elevation of cellular glutathione levels.