Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.6.99.3 (diaphorase)
 5,903 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The hepatic microsomal monooxygenase system was studied in hypophysectomized male rats exposed for 24 or 48 h to PB and/or TPA, an activator of kinase C. TPA attenuated basal and PB-induced levels of P450, aniline hydroxylase (ANH), ethylmorphine demethylase (EDM) and cytochrome c reductase. Hence, PB may effect induction via the inhibition of kinase C. Supporting this is spectral evidence that PB and TPA do not bind and the fact that TPA did not decrease P450 when co-incubated with O2 and NADPH. Hemin failed to increase P450 levels previously depressed by TPA indicating that TPA acts by lowering apocytochrome levels. This is consistent with its attenuation of PB-effected increases in hepatic RNA. TPA effects were associated with increased hepatic RNA and were blocked by puromycin.
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PMID:Cytochrome P450 induction by phenobarbital (PB) is inhibited by 12-O-tetradecanoylphorbol-13-acetate (TPA): evidence that protein kinase C regulates induction. 338

The amounts of superoxide and hydrogen peroxide generated by mitochondria under physiological conditions can be enhanced by cellular stress. This study tested the hypothesis that the response to hemin-induced stress, which includes heme oxygenase-1 (HO-1) induction, predisposes to oxidative damage of mitochondrial DNA (mtDNA). Hepatic mitochondria from control, hemin-, and CO-exposed rats were incubated with tert-butyl hydroperoxide (tert-BH) or the NO donor 1,2,3,4-oxatriazolium, 5-amino-3- (3,4-dichlorophenyl)-chloride (GEA 3162). Mitochondrial total and oxidized glutathione (GSH and GSSG), total and free iron, and 8-oxo-7, 8-dihydro-2' deoxyguanosine (8-OHdG) were determined with and without oxidants. As expected, oxidation by tert-BH induced significant GSH depletion and increased amounts of free iron and 8-OhdG. Oxidant exposure rapidly produced a large mtDNA deletion involving the coding regions for cytochrome c oxidase (COX 1) and NADH dehydrogenase (ND1 and ND2). Hemin and CO greatly exacerbated susceptibility to the deletion of mtDNA by tert-BH, and this was attenuated by preincubation with GSH methyl ester. Analysis of mitochondria-associated proteins Bax and Bcl-xl in hemin- and CO-exposed rats showed significant responses, revealing interactions with apoptotic pathways. Thus, hemin-induced mitochondrial events sensitize a specific region of the mitochondrial genome to deletion, which is related to depletion of GSH and is not explained by effects of CO. This mtDNA damage is associated with altered expression of mitochondrial cell death proteins, thereby suggesting a novel mechanism for systemic or environmental pro-oxidants to influence apoptosis.
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PMID:Rapid mtDNA deletion by oxidants in rat liver mitochondria after hemin exposure. 1182 50