Exposure of Mn and FeSODs, but not Cu/ZnSOD, to NO leads to nitrosonium and nitroxyl ions generation which cause enzyme modification and inactivation: An in vitro study

The effect of NO treatment in vitro on structural and functional alteration s of Cu/Zn, Mn, and Fe type of SODs was studied. Significant difference in response to NO of Cu/ZnSOD compared to the Mn and Fe types was demonstrated . Cu/ZnSOD was shown to be stable with respect to NO: even on prolonged exp osure, NO produced negligible effect on its structure and activity. In cont rast, both Mn and Fe types were found to be NO-sensitive: exposure to NO le d to their fast and extensive inactivation, which was accompanied by extens ive structural alterations, including (in some of the samples tested) the c leavage of enzyme polypeptide chains, presumably at His residues of the enz yme metal binding sites. The generation of nitrosonium (NO+) and nitroxyl ( NO-) ions in NO treated Mn and FeSODs, which produce enzyme modifications a nd inactivation, was demonstrated. The physiological and biomedical signifi cance of described findings is briefly discussed. (C) 1999 Elsevier Science Inc.