title: Reactive oxygen species mediate the down-regulation of mitochondrial transcripts and proteins by tumour necrosis factor-alpha in L929 cells.
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.
authors.affiliation: Laboratorio Andaluz de Biología, Universidad Pablo de Olavide, Carretera de Utrera Km 1, Sevilla 41013, Spain. jasanalc@dex.upo.es
authors.forename: José A
authors.initials: JA
authors.lastname: Sánchez-Alcázar
authors.forename: Erasmus
authors.initials: E
authors.lastname: Schneider
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Hernández-Muñoz
authors.forename: Jesús
authors.initials: J
authors.lastname: Ruiz-Cabello
authors.forename: Eva
authors.initials: E
authors.lastname: Siles-Rivas
authors.forename: Paz
authors.initials: P
authors.lastname: de la Torre
authors.forename: Belen
authors.initials: B
authors.lastname: Bornstein
authors.forename: Gloria
authors.initials: G
authors.lastname: Brea
authors.forename: Joaquín
authors.initials: J
authors.lastname: Arenas
authors.forename: Rafael
authors.initials: R
authors.lastname: Garesse
authors.forename: José A
authors.initials: JA
authors.lastname: Solís-Herruzo
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Knox
authors.forename: Plácido
authors.initials: P
authors.lastname: Navas
mesh_terms: D000818:Animals; D016923:Cell Death / Q000502:physiology; D002467:Cell Nucleus / Q000378:metabolism; D004272:DNA, Mitochondrial; D015536:Down-Regulation / Q000502:physiology; D005354:Fibrosarcoma / Q000378:metabolism; D006801:Humans; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000378:metabolism; D012333:RNA, Messenger; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D004272:DNA, Mitochondrial; D024101:Mitochondrial Proteins; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha