Antioxidant defenses in TNF-treated MCF-7 cells: Selective increase in MnSOD
Antioxidant defenses in TNF-treated MCF-7 cells: Selective increase in MnSOD
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DOI：
10.1016/s0891-5849(98)00273-1
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发表时间：
1999-04-01
影响因子：
7.4
通讯作者：
Briehl, MM
中科院分区：
文献类型：
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作者：
Siemankowski, LM;Morreale, J;Briehl, MM
氧化应激与肿瘤坏死因子-α（TNF）诱导的细胞凋亡机制有关，这引起了人们对TNF敏感细胞中抗氧化防御状态的质疑。在用TNF处理后的MCF-7细胞中检查抗氧化防御。细胞形态学和DNA片段化测定用于确认TNF处理导致的细胞凋亡增加。抗氧化防御的表达和活性分别采用北方印迹杂交分析和生化测定进行评估。五倍和十倍增加锰超氧化物歧化酶（MnSOD）mRNA的测定后，一天和五天的TNF治疗，分别。铜，锌超氧化物歧化酶，过氧化氢酶或硫氧还蛋白的表达没有改变。MnSOD活性增加约5倍后，基因表达的变化，但没有看到过氧化氢酶或谷胱甘肽过氧化物酶的活性的差异。因此，MnSOD活性的增加并不伴随着其他抗氧化防御，特别是H2 O2-清除酶的增加。MnSOD先前已显示提供针对TNF介导的细胞毒性的保护。所观察到的缺乏增加的过氧化物酶活性是一致的，与神经系统产生的超氧阴离子自由基有助于TNF诱导的细胞凋亡的机制。(C)1999 Elsevier Science Inc.
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.