In this study, we show that reactive oxygen species production induced by tumour necrosis factor α (TNF-α) 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-α had no effect on the amount of mitochondrial DNA, the results suggested that TNF-α 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-α, indicating a direct link between these two phenomena.
Reactive oxygen species mediate the down-regulation of mitochondrial transcripts and proteins by tumour necrosis factor-alpha in L929 cells
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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; Reactive oxygen species mediate the down-regulation of mitochondrial transcripts and proteins by tumour necrosis factor-alpha in L929 cells. Biochem J 1 March 2003; 370 (2): 609–619. doi: https://doi.org/10.1042/bj20021623
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