NADH-mediated DNA damage induced by a new coenzyme, pyrroloquinoline quinone, in the presence of copper(II) ion.
Pyrroloquinoline quinone (PQQ) plays a role as a vitamin or growth factor. Low concentrations of PQQ induced DNA cleavage sites frequently at thymine and cytosine residues in the presence of NADH and Cu(II). Catalase and bathocuproine inhibited DNA damage, whereas free hydroxyl radical scavengers did not. Electron spin resonance and UV-visible spectrometries showed generation of semiquinone radical and superoxide during the reaction of PQQ with NADH. These results suggest that NADH-dependent PQQ redox cycle generated superoxide and hydrogen peroxide to mediate copper-dependent DNA damage. The present study has proposed a requirement to investigate the potentiality of PQQ carcinogenicity.
Hiraku
Y
Y
Department of Public Health, Graduate School of Medicine, Kyoto University, Japan.
Kawanishi
S
S
D001483:Base Sequence; D002374:Catalase / Q000494:pharmacology; D003067:Coenzymes / Q000494:pharmacology; D003300:Copper / Q000494:pharmacology*; D004247:DNA / Q000187:drug effects*; D004249:DNA Damage; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals / Q000032:analysis; D016158:Genes, p53; D011905:Genes, ras; D006801:Humans; D007202:Indicators and Reagents; D008969:Molecular Sequence Data; D009243:NAD; D045542:PQQ Cofactor; D010618:Phenanthrolines / Q000494:pharmacology; D015363:Quinolones / Q000494:pharmacology*; D013053:Spectrophotometry; D013481:Superoxides / Q000032:analysis
D003067:Coenzymes; D005609:Free Radicals; D007202:Indicators and Reagents; D010618:Phenanthrolines; D015363:Quinolones; D009243:NAD; D013481:Superoxides; D045542:PQQ Cofactor; D003300:Copper; D004247:DNA; C002478:bathocuproine; D002374:Catalase