Oxidative aggregation of ceruloplasmin induced by hydrogen peroxide is prevented by pyruvate.
Ceruloplasmin (CP) is a blue copper glycoprotein with multiple physiological functions including ferroxidase and oxidase activities. CP is also an important serum oxygen free radical (OFR) scavenger and antioxidant, exerting cardioprotective and antifibrillatory actions. Although it has been reported that CP activities can be inhibited by OFR, the intimate mechanism of this inactivation is still not clear. Exposure of bovine CP to H2O2 induced inactivation of the protein as well as structural alterations as indicated by loss of protein bands by SDS-PAGE. Both phenomena were H2O2 concentration and time dependent. HPLC gel filtration and capillary electrophoresis analysis of CP treated with H2O2 revealed an aggregation of the protein. Quantification of dityrosine formation by fluorescence indicated the involvement of dityrosine bridging, which could be responsible for aggregation of CP under oxidative attack. Oxidative damage to CP under H2O2 treatment was completely prevented by pyruvate, suggesting that the association of CP with antioxidants could extend the range of the protective action of this protein.
Aouffen
M'hammed
M
Department of Chemistry and Biochemistry, Université du Québec à Montreal, C.P. 8888, Succ. Centre-ville, Montreal, Qué., Canada H3C 3P8.
Paquin
Joanne
J
Furtos
Alexandra
A
Waldron
Karen C
KC
Mateescu
Mircea-Alexandru
MA
D000818:Animals; D002417:Cattle; D002570:Ceruloplasmin / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism*; D002850:Chromatography, Gel / Q000379:methods; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004305:Dose-Response Relationship, Drug; D019075:Electrophoresis, Capillary / Q000379:methods; D016166:Free Radical Scavengers / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D016877:Oxidants / Q000494:pharmacology*; D011489:Protein Denaturation; D019289:Pyruvic Acid / Q000494:pharmacology*; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism
D016166:Free Radical Scavengers; D016877:Oxidants; D014443:Tyrosine; D019289:Pyruvic Acid; D006861:Hydrogen Peroxide; C007543:dityrosine; D002570:Ceruloplasmin