Strain difference of cadmium accumulation by liver slices of inbred Wistar-Imamichi and Fischer 344 rats.

Strain difference in the accumulation of cadmium (Cd) by liver slices was examined in inbred Cd-resistant Wistar-Imamichi (WI) and Cd-sensitive Fischer 344 (F344) rats. The accumulation of Cd by liver slices of WI rats was significantly lower than that of F344 rats, suggesting strain-related differences in the transport of Cd into the liver cells of these two rat strains. In addition, a similar strain difference was observed in the accumulation of zinc (Zn) by liver slices from WI and F344 rats. Cd accumulation by F344 liver slices decreased when Zn was added to the medium in combination with Cd. Furthermore, in F344 liver slices, Zn accumulation was significantly decreased when Cd was added to the medium. These results suggest that the accumulation of Cd by the liver is probably mediated, at least in part, by Zn transport systems. However, we found no strain difference in hepatic ZnT3 or ZIP3 transcript levels between WI and F344 rats. Further work is in progress to identify the transporter that causes the strain differences in hepatic Cd accumulation seen with WI and F344 rats.

Stereoselective reduction of 4-benzoylpyridine in the heart of vertebrates.

The stereoselectivity in the reduction of 4-benzoylpyridine (4-BP) was examined in the cytosolic fractions from the heart of 9 vertebrates (pig, rabbit, guinea pig, rat, mouse, chicken, soft-shelled turtle, frog and flounder). 4-BP was stereoselectively reduced to S(-)-alpha-phenyl-4-pyridylmethanol [S(-)-PPOL] in the cytosolic fractions from the heart of pig, rabbit and guinea pig. However, of mammalian heart cytsol tested, only rat heart cytosol had little ability to reduce stereoselectively 4-BP. In an attempt to elucidate this reason, amino acid sequence of rat heart carbonyl reductase (RatHCR) was deduced from the cloned cDNA and compared with that of pig heart carbonyl reductase (PigHCR), which shows a high stereoselectivity in the reduction of 4-BP to S(-)-PPOL. RatHCR showed a high identity with PigHCR in amino acid sequence. Furthermore, recombinant RatHCR was confirmed to reduce stereoselectively 4-BP to S(-)-PPOL with a high optical purity comparable to recombinant PigHCR. It is possible that in the cytosolic fraction from the heart of rat, constitutive reductase other than RatHCR counteracts the stereoselective reduction of 4-BP to S(-)-PPOL, by catalyzing the reduction of 4-BP to the R(+)-enantiomer.

Effects of quinones and flavonoids on the reduction of all-trans retinal to all-trans retinol in pig heart.

We have recently purified a tetrameric carbonyl reductase from the cytosolic fraction of pig heart (pig heart carbonyl reductase). Since pig heart carbonyl reductase efficiently reduces all-trans retinal as the endogenous substrate, it probably plays an important role in retinoid metabolism in the heart. The purpose of the present study was to evaluate the inhibitory effects of quinones and flavonoids on the reduction of all-trans retinal to all-trans retinol catalyzed by pig heart carbonyl reductase, using pig heart cytosol. Of quinones tested, 9,10-phenanthrenequinone, a component of diesel exhaust particles, was the most potent inhibitor for the all-trans retinal reduction, and a significant inhibition was also observed for plumbagin and menadione. The order of the inhibitory potencies for flavonoids was kaempferol > quercetin > genistein > myricetin = apigenin = daidzein. However, the inhibitory potencies of flavonoids were much lower than that of 9,10-phenanthrenequinone. 9,10-Phenanthrenequinone competitively inhibited the all-trans retinal reduction, whereas kaempferol exhibited a mixed-type inhibition. It is likely that 9,10-phenanthrenequinone strongly inhibits the reduction of all-trans retinal to all-trans retinol by acting as the substrate inhibitor of pig heart carbonyl reductase present in pig heart cytosol.