Protective effects of carnosine, homocarnosine and anserine against peroxyl radical-mediated Cu,Zn-superoxide dismutase modification.
Carnosine (beta-alanyl-L-histidine), homocarnosine (gamma-amino-butyryl-L-histidine) and anserine (beta-alanyl-1-methyl-L-histidine) have been proposed to act as anti-oxidants in vivo. The protective effects of carnosine and related compounds against the oxidative damage of human Cu,Zn-superoxide dismutase (SOD) by peroxyl radicals generated from 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH) were studied. The oxidative damage to Cu,Zn-SOD by AAPH-derived radicals led to protein fragmentation, which is associated with the inactivation of enzyme. Carnosine, homocarnosine and anserine significantly inhibited the fragmentation and inactivation of Cu,Zn-SOD by AAPH. All three compounds also inhibited the release of copper ions from the enzyme and the formation of carbonyl compounds in AAPH-treated Cu,Zn-SOD. These compounds inhibited the fragmentation of other protein without copper ion. The results suggest that carnosine and related compounds act as the copper chelator and peroxyl radical scavenger to protect the protein fragmentation. Oxidation of amino acid residues in Cu,Zn-SOD induced by AAPH were significantly inhibited by carnosine and related compounds. It is proposed that carnosine and related dipeptides might be explored as potential therapeutic agents for pathologies that involve Cu,Zn-SOD modification mediated by peroxyl radicals.
Kang
Jung Hoon
JH
Department of Genetic Engineering, Division of Natural Sciences, Chongju University, 360-764, South Korea. jhkang@chongju.ac.kr
Kim
Kyung Sik
KS
Choi
Soo Young
SY
Kwon
Hyeok Yil
HY
Won
Moo Ho
MH
Kang
Tae-Cheon
TC
D000578:Amidines; D000861:Anserine / Q000494:pharmacology*; D002336:Carnosine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002374:Catalase / Q000737:chemistry; D002614:Chelating Agents / Q000737:chemistry; D016166:Free Radical Scavengers / Q000737:chemistry; D005609:Free Radicals / Q000037:antagonists & inhibitors / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D016877:Oxidants; D010084:Oxidation-Reduction; D010545:Peroxides / Q000037:antagonists & inhibitors / Q000737:chemistry*; D013482:Superoxide Dismutase / Q000037:antagonists & inhibitors* / Q000737:chemistry; D013997:Time Factors
D000578:Amidines; D002614:Chelating Agents; D016166:Free Radical Scavengers; D005609:Free Radicals; D016877:Oxidants; D010545:Peroxides; C049375:perhydroxyl radical; C005038:homocarnosine; C046728:2,2'-azobis(2-amidinopropane); D002336:Carnosine; D002374:Catalase; D013482:Superoxide Dismutase; D000861:Anserine