Reactive oxygen species mediate the down-regulation of mitochondrial transcripts and proteins by tumour necrosis factor-alpha in L929 cells.
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| Abstract |
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.
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| Authors | José A Sánchez-Alcázar, Erasmus Schneider, Inmaculada Hernández-Muñoz, Jesús Ruiz-Cabello, Eva Siles-Rivas, Paz de la Torre, Belen Bornstein, Gloria Brea, Joaquín Arenas, Rafael Garesse, José A Solís-Herruzo, Alan J Knox, Plácido Navas |
| Journal | The Biochemical journal (Biochem J) Vol. 370 Issue Pt 2 Pg. 609-19 (Mar 01 2003) ISSN: 0264-6021 [Print] England |
| PMID | 12470298 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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