Involvement of carbonyl reductase in superoxide formation through redox cycling of adrenochrome and 9,10-phenanthrenequinone in pig heart.
The effects of adrenochrome, a metabolite of epinephrine (adrenaline), and 9,10-phenanthrenequinone (PQ), a component of diesel exhaust particles, on the stereoselective reduction of 4-benzoylpyridine (4-BP) were examined in pig heart cytosol. PQ was a potent inhibitor for the 4-BP reduction, while adrenochrome was a poor inhibitor. A similar result was observed in the effects of adrenochrome and PQ on the reduction of all-trans retinal. Furthermore, although PQ mediated efficiently the formation of superoxide anion radical through its redox cycling in pig heart cytosol, adrenochrome had no ability to mediate the superoxide formation. These may be because the reactivity for adrenochrome, catalyzed by pig heart carbonyl reductase (PHCR), is much lower than that for PQ. The optimal pH for the reduction of PQ in pig heart cytosol was around 5.5. Dicumarol, a potent inhibitor of DT-diaphorase, had little effect on the time course of NADPH oxidation during the reduction of PQ. Therefore, it is concluded that PHCR plays a critical role in superoxide formation through redox cycling of PQ.
Oginuma
Michiko
M
Faculty of Education, Kumamoto University, 2-40-1, Kurokami, Kumamoto 860-8555, Japan.
Shimada
Hideaki
H
Imamura
Yorishige
Y
D000323:Adrenochrome / Q000378:metabolism* / Q000633:toxicity*; D000429:Alcohol Oxidoreductases / Q000378:metabolism*; D000449:Aldehyde Reductase; D000074408:Aldo-Keto Reductases; D000818:Animals; D003600:Cytosol / Q000378:metabolism; D001728:Dicumarol / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006321:Heart / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007700:Kinetics; D009206:Myocardium / Q000378:metabolism*; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000037:antagonists & inhibitors; D009249:NADP / Q000378:metabolism; D010084:Oxidation-Reduction; D010616:Phenanthrenes / Q000378:metabolism* / Q000633:toxicity*; D011725:Pyridines / Q000737:chemistry / Q000378:metabolism; D012172:Retinaldehyde / Q000737:chemistry / Q000378:metabolism; D013237:Stereoisomerism; D013481:Superoxides / Q000378:metabolism; D034421:Sus scrofa; D001335:Vehicle Emissions / Q000633:toxicity
D004791:Enzyme Inhibitors; D010616:Phenanthrenes; D011725:Pyridines; D001335:Vehicle Emissions; D013481:Superoxides; C005399:9,10-phenanthrenequinone; C066738:4-benzoylpyridine; D009249:NADP; D000323:Adrenochrome; D001728:Dicumarol; D000429:Alcohol Oxidoreductases; D000074408:Aldo-Keto Reductases; D000449:Aldehyde Reductase; D016660:NAD(P)H Dehydrogenase (Quinone); D012172:Retinaldehyde