Cytochrome c Oxidase Subunit III A MOLECULAR MARKER FORN-(4-HYDROXYPHENYL)RETINAMIDE-INDUCED OXIDATIVE STRESS IN HEPATOMA CELLS

摘要: N-(4-hydroxyphenyl)retinamide (4HPR), a chemopreventive and chemotherapeutic retinoid, induces apoptosis in various types of cells. Currently, oxidative mitochondrial damage is thought to cause 4HPR-induced apoptosis, although the exact mechanism has not yet been clarified. 4HPR effectively hepatoma cells susceptibility differs cell-specific manner. Hep-3B PLC/PRF/5 were more susceptible than Hep-G2 SK-HEP-1 cells, resistance seems be related growth inhibition (G1 arrest). We further observed that specifically down-regulates cytochrome coxidase subunit III (CO III) transcript levels through destabilization its mRNA thus decreases activity c oxidase (complex IV). To explore whereby CO was decreased by 4HPR, we used adenine nucleotide translocator (ANT) ligands, which modulate transmembrane potential (ΔΨm) without altering transcription. Intriguingly, bongkrekic acid, specific ANT inhibitor, enhanced ΔΨm disruption, turn level ofCO transcripts, accompanied increases generation reactive oxygen species apoptosis. In contrast, atractyloside, an activator ANT, inhibited those effects. Taken together, these results indicate down-regulation III, molecular marker stress, may result from upstream disruption ligands capable modulating stress