9,10-phenanthrenequinone, a component of diesel exhaust particles, inhibits the reduction of 4-benzoylpyridine and all-trans-retinal and mediates superoxide formation through its redox cycling in pig heart.
We have recently purified a tetrameric carbonyl reductase from the cytosolic fraction of pig heart (pig heart carbonyl reductase, PHCR), using 4-benzoylpyridine (4-BP) as the substrate. PHCR has the ability to catalyze efficiently the reduction of 9,10-phenanthrenequinone (PQ) contained in diesel exhaust particles (DEPs). Thus, the present study was attempted to characterize the inhibitory effect of PQ on the reduction of 4-BP and all-trans-retinal in pig heart cytosol. Of the DEP components examined, PQ was the most potent inhibitor for the reduction of 4-BP and all-trans-retinal in pig heart cytosol. PQ also inhibited competitively the 4-BP reduction. These results indicate that PQ inhibits the reduction of 4-BP and all-trans-retinal by acting PHCR present in pig heart cytosol. Furthermore, whether PQ induces the formation of superoxide anion radical was examined in pig heart cytosol. The absorbance of cytochrome c at 550 nm was increased with the time by adding PQ, and the increased absorbance was decreased in the presence of superoxide dismutase. A similar result was observed in the reaction system of recombinant PHCR. On the basis of these results, it is concluded that PQ not only inhibits the reduction of 4-BP and all-trans-retinal catalyzed by PHCR but also mediates superoxide formation through its redox cycling involved in PHCR. We propose the possibility that PQ disturbs the homeostasis of retinoid metabolism and induces oxidative stress in pig heart.
Shimada
Hideaki
H
Faculty of Education, Kumamoto University, 2-40-1, Kurokami, Kumamoto 860-8555, Japan.
Oginuma
Michiko
M
Hara
Akira
A
Imamura
Yorishige
Y
D000393:Air Pollutants / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D006321:Heart / Q000187:drug effects*; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism; D010084:Oxidation-Reduction; D010616:Phenanthrenes / Q000378:metabolism / Q000494:pharmacology*; D011725:Pyridines / Q000378:metabolism*; D013237:Stereoisomerism; D013481:Superoxides / Q000378:metabolism*; D013552:Swine; D001335:Vehicle Emissions; D014801:Vitamin A / Q000378:metabolism*
D000393:Air Pollutants; D010616:Phenanthrenes; D011725:Pyridines; D001335:Vehicle Emissions; D013481:Superoxides; D014801:Vitamin A; C005399:9,10-phenanthrenequinone; C066738:4-benzoylpyridine