title: Modification and inactivation of Cu,Zn-superoxide dismutase by the lipid peroxidation product, acrolein.
abstract: Acrolein is the most reactive aldehydic product of lipid peroxidation and is found to be elevated in the brain when oxidative stress is high. The effects of acrolein on the structure and function of human Cu,Zn-superoxide dismutase (SOD) were examined. When Cu,Zn-SOD was incubated with acrolein, the covalent crosslinking of the protein was increased, and the loss of enzymatic activity was increased in a dose-dependent manner. Reactive oxygen species (ROS) scavengers and copper chelators inhibited the acrolein-mediated Cu,Zn-SOD modification and the formation of carbonyl compound. The present study shows that ROS may play a critical role in acrolein-induced Cu,Zn-SOD modification and inactivation. When Cu,Zn-SOD that has been exposed to acrolein was subsequently analyzed by amino acid analysis, serine, histidine, arginine, threonine and lysine residues were particularly sensitive. It is suggested that the modification and inactivation of Cu,Zn-SOD by acrolein could be produced by more oxidative cell environments.
authors.affiliation: Department of Genetic Engineering, Cheongju University, Cheongju 360-764, Korea jhkang@cju.ac.kr.
authors.forename: Jung Hoon
authors.initials: JH
authors.lastname: Kang
mesh_terms: D000171:Acrolein / Q000737:chemistry* / Q000494:pharmacology*; D000596:Amino Acids / Q000032:analysis; D002614:Chelating Agents / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D003300:Copper / Q000737:chemistry / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D016166:Free Radical Scavengers / Q000494:pharmacology; D006801:Humans; D050050:Protein Carbonylation / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics; D013482:Superoxide Dismutase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
chemical_list: D000596:Amino Acids; D002614:Chelating Agents; D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D011994:Recombinant Proteins; D000171:Acrolein; D003300:Copper; D013482:Superoxide Dismutase