Generation of alloxan radical in rat islet cells: participation of NADPH: cytochrome P-450 reductase.
Cytotoxic actions of alloxan are thought to be caused by the hydroxyl radical (HO+) generated in a cyclic reaction involving alloxan and its reduction product, alloxan radical (HA+). The generation of HA+ and the oxidation of reduced nicotinamide adenine dinucleotide phosphate (NADPH) were observed in the reaction system of alloxan with NADPH in the presence of purified NADPH: cytochrome P-450 reductase [EC 1.6.2.4] (fp2) from rat liver microsomes. Both the generation of HA+ and the oxidation of NADPH were increased with increasing the concentrations of alloxan or fp2. These results indicate that NADPH-linked HA+ generation was catalyzed by fp2. The HA+ was generated in the reaction of alloxan with a homogenate of rat islet cells. The generation of HA+ in the reaction of alloxan with the homogenate of rat islet cells was markedly diminished by an immunogloblin fraction (Ig) of anti-fp2 serum, but not by control-Ig. The anti-fp2-Ig also inhibited the generation of HA+ in the reaction system of alloxan with NADPH in the presence of fp2. When the homogenate of islet cells from phenobarbital-treated rats was used, the generation of HA+ was significantly increased in comparison with that from the control rats. However, the homogenate of islet cells from 3-methylcholanthrene-treated rats did not have such a stimulative effect. These results suggest that the reduction of alloxan to HA+ was catalyzed by fp2 presented in islet cells.
Sakurai
K
K
Hokkaido Institute of Pharmaceutical Sciences, Otaru, Japan.
Ogiso
T
T
D000496:Alloxan / Q000378:metabolism*; D000818:Animals; D002384:Catalysis; D002478:Cells, Cultured; D004578:Electron Spin Resonance Spectroscopy; D004591:Electrophoresis, Polyacrylamide Gel; D017665:Hydroxyl Radical; D007136:Immunoglobulins / Q000276:immunology; D007515:Islets of Langerhans / Q000166:cytology / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D009249:NADP / Q000378:metabolism*; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism*; D010084:Oxidation-Reduction; D051381:Rats; D017208:Rats, Wistar
D007136:Immunoglobulins; D017665:Hydroxyl Radical; D009249:NADP; D000496:Alloxan; D009251:NADPH-Ferrihemoprotein Reductase