Antioxidant defenses in TNF-treated MCF-7 cells: Selective increase in MnSOD

被引:47
作者
Siemankowski, LM [1 ]
Morreale, J [1 ]
Briehl, MM [1 ]
机构
[1] Univ Arizona, Dept Pathol, Tucson, AZ 85724 USA
关键词
tumor necrosis factor-alpha; MCF-7; cells; apoptosis; antioxidant defenses; gene expression; enzyme activity; oxidative stress; free radical;
D O I
10.1016/S0891-5849(98)00273-1
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Oxidative stress has been implicated in the mechanism of tumor necrosis factor-alpha (TNF)-induced apoptosis, raising a question about the status of antioxidant defenses in TNF-sensitive cells. Antioxidant defenses were examined in MCF-7 cells after treatment with TNF. Cell morphology and DNA fragmentation assays were used to confirm increased apoptosis as a result of TNF treatment. The expression and activity of antioxidant defenses were assessed using Northern blot hybridization analyses and biochemical assays, respectively. Five- and ten-fold increases in manganese superoxide dismutase (MnSOD) mRNA were measured after one and five days of TNF treatment, respectively. The expression of copper,zinc superoxide dismutase, catalase or thioredoxin was not altered. An approximate five-fold increase in MnSOD activity followed the change in gene expression, but no difference in the activity of catalase or glutathione peroxidase was seen. Thus, increased MnSOD activity was not accompanied by an increase in other antioxidant defenses and in particular, H2O2-scavenging enzymes. MnSOD has previously been shown to afford protection against TNF-mediated cytotoxicity. The observed lack of increased peroxidase activity is consistent with mitochondrially-generated superoxide anion radical contributing to the mechanism of TNF-induced apoptosis. (C) 1999 Elsevier Science Inc.
引用
收藏
页码:919 / 924
页数:6
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