Tumor necrosis factor-alpha increases Mn-SOD expression: protection against oxidant injury.
Tumor necrosis factor-alpha increases Mn-SOD expression: protection against oxidant injury.
复制标题
肿瘤坏死因子-α 增加 Mn-SOD 表达：防止氧化损伤。
DOI：
10.1152/ajplung.1991.260.4.l296
复制
发表时间：
1991
期刊：
影响因子：
--
通讯作者：
Wispe,JR
中科院分区：
文献类型：
--
作者：
Warner,BB;Burhans,MS;Clark,JC;Wispe,JR
抗氧化酶，包括超氧化物歧化酶，对保护肺部免受氧损伤很重要。锰超氧化物歧化酶（Mn-SOD）是一种位于线粒体的超氧阴离子（O2-）清除剂，线粒体是O2-的主要位点。在高氧条件下产生。我们研究了巨噬细胞来源的细胞因子肿瘤坏死因子（tnf - α）对人肺腺癌细胞中Mn-SOD表达的影响。tnf - α显著增加Mn-SOD活性和mRNA，呈剂量和时间依赖性。tnf - α (25 ng/ml)作用48小时后，Mn-SOD活性增加3倍，mRNA活性增加20倍。为了研究这种增加的机制，将细胞与tnf - α (25 ng/ml)(含或不含环己亚胺（10微米）或放线菌素D（10微克/ml）孵育48小时。放线菌素D能抑制tnf - α对Mn-SOD mRNA的诱导，而环己亚胺不能。这些发现表明，tnf - α的作用需要基因转录，而不需要合成新的蛋白质中间体。为了验证Mn-SOD升高对氧化损伤的保护作用，我们将肺腺癌细胞在tnf - α (25 ng/ml)中孵育48小时，然后暴露于细胞内O2-的百草枯（PQ+）中。发电机。与对照组相比，经tnf - α预处理的PQ+细胞的存活率显著提高。在LD50（6微米）下，对照细胞95%的tnf α处理细胞存活，LD75（10微米）下85%存活，LD90（14微米）下77%存活。我们的研究结果表明，tnf - α在肺腺癌细胞中诱导Mn-SOD是翻译前介导的，tnf - α增加Mn-SOD活性可以保护肺腺癌细胞免受O2自由基的侵害。
Antioxidant enzymes, including superoxide dismutase, are important for protecting the lung against O2 injury. Manganese superoxide dismutase (Mn-SOD) is a superoxide anion (O2-.) scavenger located in the mitochondria, a primary site of O2-. production during hyperoxia. We studied the effects of tumor necrosis factor (TNF-alpha), a macrophage-derived cytokine, on Mn-SOD expression in human pulmonary adenocarcinoma cells. TNF-alpha significantly increased Mn-SOD activity and mRNA in a dose-and time-dependent manner. Mn-SOD activity was increased 3-fold and mRNA 20-fold after a 48-h incubation with TNF-alpha (25 ng/ml). To examine the mechanism of this increase, cells were incubated for 48 h with TNF-alpha (25 ng/ml) with or without cycloheximide (10 microns) or actinomycin D (10 micrograms/ml). Actinomycin D blocked the induction of Mn-SOD mRNA by TNF-alpha, but cycloheximide did not. These findings suggest that the effect of TNF-alpha requires gene transcription but not synthesis of new protein intermediates. To test the hypothesis that increased Mn-SOD protects against oxidative injury, pulmonary adenocarcinoma cells were incubated in TNF-alpha (25 ng/ml) for 48 h and then exposed to paraquat (PQ+), an intracellular O2-. generator. Cells pretreated with TNF-alpha had significantly improved survival in PQ+ compared with controls. At the LD50 (6 microns) for control cells, 95% of TNF-alpha-treated cells survived, 85% at the LD75 (10 microns), and 77% at the LD90 (14 microns). Our results suggest that the induction of Mn-SOD by TNF-alpha in pulmonary adenocarcinoma cells is pretranslationally mediated and that increasing Mn-SOD activity with TNF-alpha confers protection against O2 radicals.