Reactive oxygen species mediate the down-regulation of mitochondrial transcripts and proteins by tumour necrosis factor-alpha in L929 cells.

Reactive oxygen species mediate the down-regulation of mitochondrial transcripts and proteins by tumour necrosis factor-alpha in L929 cells.
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在 L929 细胞中,活性氧通过肿瘤坏死因子-α 介导线粒体转录物和蛋白质的下调。

DOI:
10.1042/bj20021623
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发表时间:
2003
期刊:
The Biochemical journal
影响因子:
--
通讯作者:
P. Navas
P. Navas
中科院分区:
--
文献类型:
--
作者:
J. Sánchez;E. Schneider;I. Hernández;J. Ruíz;Eva Siles;P. de la Torre;B. Bornstein;Gloria Brea;J. Arenas;R. Garesse;J. Solís;A. Knox;P. Navas

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在这项研究中,我们证明了肿瘤坏死因子α(TNF-α)诱导的L929细胞中活性氧的产生与线粒体转录ATPase 6-8的稳态mRNA水平的下降有关。同时,甘油醛-3-磷酸脱氢酶和磷酸果糖激酶两种核糖酵解酶的转录水平也增加。这些变化与线粒体ATPase 6基因编码的ATPase亚单位a和细胞色素c氧化酶亚单位II的蛋白水平降低以及磷酸果糖激酶的蛋白水平升高有关。由于肿瘤坏死因子-α对线粒体DNA的含量没有影响,结果提示肿瘤坏死因子-α在转录和/或转录后水平起作用。活性氧清除剂,如丁基羟基苯甲醚和丁基羟基甲苯,可以阻止自由基的产生,阻止ATPase 6-8转录下调,保持ATPase a亚基和细胞色素c氧化酶亚基II的蛋白水平,并减弱对肿瘤坏死因子-α的细胞毒性反应,表明这两种现象之间存在直接联系。
In this study, we show that reactive oxygen species production induced by tumour necrosis factor alpha (TNF-alpha) in L929 cells was associated with a decrease in the steady-state mRNA levels of the mitochondrial transcript ATPase 6-8. Simultaneously, the transcript levels of two nuclear-encoded glycolytic enzymes, glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and phosphofructokinase, were increased. These changes were associated with decreased protein levels of the ATPase subunit a (encoded by the mitochondrial ATPase 6 gene) and cytochrome c oxidase subunit II, and increased protein levels of phosphofructokinase. Since TNF-alpha had no effect on the amount of mitochondrial DNA, the results suggested that TNF-alpha acted at the transcriptional and/or post-transcriptional level. Reactive oxygen species scavengers, such as butylated hydroxianisole and butylated hydroxytoluene, blocked the production of free radicals, prevented the down-regulation of ATPase 6-8 transcripts, preserved the protein levels of ATPase subunit a and cytochrome c oxidase subunit II, and attenuated the cytotoxic response to TNF-alpha, indicating a direct link between these two phenomena.
抗癌药物会在细胞死亡前诱导线粒体细胞色素 c 表达增加。
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