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Closed Access item Reactive oxygen species mediate the down-regulation of mitochondrial transcripts and proteins by tumour necrosis factor-a in L929 cells

Authors:Sánchez-Alcázar, José Antonio
Bornstein, Belén
Arenas, Joaquín
Garesse, Rafael
Navas, Plácido
Keywords:ATPase 6-8, Free radical, Glycolysis, Mitochondrial transcript, necrosis, Tumour necrosis factor a (TNF-a)
Issue Date:Mar-2003
Publisher:Portland Press
Citation:Biochemical Journal 370(2): 609-619 (2003)
Abstract:In this study, we show that reactive oxygen species production induced by tumour necrosis factor a (TNF-a) 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-a had no effect on the amount of mitochondrial DNA, the results suggested that TNF-a 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-a, indicating a direct link between these two phenomena.
Description:11 pages, 10 figures.
Publisher version (URL):http://www.biochemj.org/bj/370/0609/bj3700609.htm
Appears in Collections:(IIBM) Artículos

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