title: Age-dependent oxidation and aggregation of ZnT-1: a role for metal catalyzed oxidation?
abstract: Biological aging is associated with the oxidation and/or aggregation of a variety of proteins, which may contribute to the age-dependent loss of function. Protein modification can be caused by multiple chemical mechanisms, which may selectively target specific proteins. Here we show that the ZnT-1 isoform of the family of cation diffusion facilitators suffers age-dependent oxidation and covalent aggregation. Parallel in vitro experiments with a plasma membrane-rich fraction and recombinant ZnT-1 suggest that ZnT-1 aggregation may be caused by metal-catalyzed oxidation (MCO). The latter would be consistent with the known propensity of metal-binding proteins to suffer MCO.
authors.affiliation: Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, KS 66047, USA.
authors.forename: Vikram
authors.initials: V
authors.lastname: Sadineni
authors.forename: Christian
authors.initials: C
authors.lastname: Schöneich
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western / Q000379:methods; D002384:Catalysis; D027682:Cation Transport Proteins; D002462:Cell Membrane / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D008670:Metals / Q000378:metabolism*; D036103:Nanotechnology; D010084:Oxidation-Reduction; D030421:Peroxynitrous Acid / Q000494:pharmacology; D051381:Rats; D011914:Rats, Inbred BN; D011916:Rats, Inbred F344; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D027682:Cation Transport Proteins; D008565:Membrane Proteins; D008670:Metals; D030421:Peroxynitrous Acid; C092392:Slc30a1 protein, rat; D006861:Hydrogen Peroxide