Ferritin enhances salsolinol-mediated DNA strand breakage: protection by carnosine and related compounds.
Salsolinol is an endogenous neurotoxin, known to be involved in the pathogenesis of neurodegenerative disorders. In this present study, we have attempted to characterize the oxidative damage of DNA induced by the reaction of salsolinol with ferritin. When DNA was incubated with salsolinol and ferritin, DNA strand breakage occurred. Hydroxyl radical scavengers and catalase reduced salsolinol/ferritin system-mediated DNA cleavage, whereas Cu,Zn-superoxide dismutase did not inhibit DNA cleavage. The reaction of salsolinol with ferritin resulted in a time-dependent increase in the release of free iron ions. A strong iron chelator, ferrozine, effectively inhibited the salsolinol/ferritin system-mediated DNA cleavage. Ferritin enhanced a mutation of the lacZ' gene in the presence of salsolinol when measured as a loss of alpha-complementation. These results indicate that salsolinol/ferritin system-mediated DNA cleavage and mutation may be attributable to hydroxyl radical generation via the Fenton-like reaction of free iron ions released from oxidatively damaged ferritin. The endogenous dipeptides, carnosine and related compounds, are naturally occurring compounds with a multiplicity of neuroprotective properties. Carnosine, homocarnosine and anserine significantly inhibited salsolinol/ferritin system-mediated DNA strand breakage and mutation. These results indicate that carnosine and related compounds effectively suppressed the salsolinol/ferritin system-mediated DNA strand breakage via hydroxyl radical scavenging.
Kang
Jung Hoon
JH
Department of Genetic Engineering, Cheongju University, Cheongju 360-764, Republic of Korea. jhkang@cju.ac.kr
D000861:Anserine / Q000378:metabolism; D002336:Carnosine / Q000031:analogs & derivatives / Q000378:metabolism*; D002374:Catalase / Q000378:metabolism; D053904:DNA Breaks, Single-Stranded; D004278:DNA, Superhelical / Q000187:drug effects / Q000378:metabolism*; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D005293:Ferritins / Q000378:metabolism*; D005297:Ferrozine / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000378:metabolism; D006878:Hydroxides / Q000378:metabolism; D007502:Iron Chelating Agents / Q000494:pharmacology; D007546:Isoquinolines / Q000378:metabolism*; D007763:Lac Operon; D009154:Mutation; D018384:Oxidative Stress / Q000187:drug effects; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors
D004278:DNA, Superhelical; D016166:Free Radical Scavengers; D006878:Hydroxides; D007502:Iron Chelating Agents; D007546:Isoquinolines; D005297:Ferrozine; C005038:homocarnosine; D002336:Carnosine; D005293:Ferritins; C031356:hydroxide ion; C036617:salsolinol; D002374:Catalase; D013482:Superoxide Dismutase; D000861:Anserine