Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.9.3.1 (cytochrome oxidase)
 8,822 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cytochrome c oxidase (EC 1.9.3.1) is an enzyme which is composed of subunits derived from both the mitochondrial and the nuclear genomes. To determine whether or not the expression of these two genomes is co-ordinated at the mRNA level, we have examined the steady-state levels of mRNAs coding for cytochrome c oxidase subunit III (mitochondrially encoded) and subunit VIc (nuclear-encoded) in rat tissues. This was compared with the tissue concentration of the holoenzyme, which was estimated by measuring cytochrome c oxidase enzyme activity. The tissues (heart, brain, liver, kidney, soleus muscle and superficial white vastus muscle) possessed a 13-fold range of enzyme activity, which was highest in heart and lowest in the superficial vastus muscle. Specific subunit mRNA levels were quantified by using slot-blot hybridization of cDNA probes to total tissue RNA. The highest values for subunit III and Vlc mRNA tissue contents were found in kidney, followed by liver and heart (40-60% of that of kidney). The white vastus muscle contained the lowest subunit mRNA level (15% of that of kidney). Although some variability was apparent within each tissue, a parallel pattern of mRNA expression of the nuclear- and mitochondrially encoded subunits was observed. Differences between muscle (heart, vastus and soleus) and non-muscle tissues were noted in the relationship between mRNA and protein levels of expression. Thus, although this suggests that tissue-specific regulatory processes operate, the steady-state expression of subunit III and subunit Vlc mRNAs appears to be co-ordinately regulated.
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PMID:Co-ordinate expression of cytochrome c oxidase subunit III and VIc mRNAs in rat tissues. 216 71

It is believed that one cause of sperm dysfunction might arise through multiple mitochondrial DNA deletions (Delta mtDNA) resulting in the formation of an incomplete electron transport chain. This study investigates the incidence of multiple Delta mtDNA in human spermatozoa prepared on Percoll gradients. Firstly, we investigated for the presence of two frequently analysed Delta mtDNA, the 4977 and 7.4 kb deletions, using conventional polymerase chain reaction (PCR). These two deletions are characteristically flanked by direct repeats. We further analysed the incidence of one other deletion, the 15 bp deletion in the cytochrome c oxidase subunit III (COX III) of complex IV to determine whether other deletions flanked by direct repeats could be equally predictive. The incidence of these three deletions was not clearly associated with the diagnostic categorization of male infertility. However, the use of long PCR showed that samples harbouring high numbers of Delta mtDNA were associated with the diagnostic categorization of male infertility. We propose that these deletions could arise through a free radical-driven event occurring at the spermatogonial cell stage resulting in the replication of Delta mtDNA molecules at the expense of wild-type molecules. These anomalies in ejaculated sperm mtDNA could account for reproductive failure in some men.
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PMID:Men with oligoasthenoteratozoospermia harbour higher numbers of multiple mitochondrial DNA deletions in their spermatozoa, but individual deletions are not indicative of overall aetiology. 1113 67

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 induces apoptosis in hepatoma cells although the susceptibility differs in a cell-specific manner. Hep-3B and PLC/PRF/5 cells were more susceptible to 4HPR than were Hep-G2 and SK-HEP-1 cells, and the resistance to 4HPR seems to be related to growth inhibition (G(1) arrest). We further observed that 4HPR specifically down-regulates cytochrome c oxidase subunit III (CO III) transcript levels through destabilization of its mRNA and thus decreases the activity of cytochrome c oxidase (complex IV). To explore the mechanism whereby the CO III transcript was decreased by 4HPR, we used adenine nucleotide translocator (ANT) ligands, which modulate mitochondrial transmembrane potential (deltapsi(m)) without altering CO III transcription. Intriguingly, bongkrekic acid, a specific ANT inhibitor, enhanced 4HPR-induced deltapsi(m) disruption, which in turn decreased the level of CO III transcripts, which was accompanied by increases in the generation of reactive oxygen species and in apoptosis. In contrast, atractyloside, an activator of ANT, inhibited those 4HPR-induced effects. Taken together, these results indicate that down-regulation of CO III, a molecular marker of oxidative stress, may result from upstream deltapsi(m) disruption and that ligands of ANT may be capable of modulating 4HPR-induced oxidative stress and apoptosis.
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PMID:Cytochrome c oxidase subunit III: a molecular marker for N-(4-hydroxyphenyl)retinamise-induced oxidative stress in hepatoma cells. 1169 12