期刊
FREE RADICAL BIOLOGY AND MEDICINE
卷 37, 期 12, 页码 2018-2026出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2004.08.026
关键词
free radicals; human copper; zinc superoxide dismutase; carbonate radical; trytophan oxidation; kynurenine; N-forrnyl kynurenine; amyotrophic lateral sclerosis
资金
- NIBIB NIH HHS [EB001980] Funding Source: Medline
- NINDS NIH HHS [NS40494] Funding Source: Medline
Previously, we showed that oxidation of tryptophan-32 (Trp-32) residue was crucial for H2O2/bicarbonate (HCO3-)-dependent covalent aggregation of human Cu,Zn SOD1 (hSOD1). The carbonate anion radical (CO3.-)-induced oxidation of Trp-32 to kynurenine-type oxidation products was proposed to cause the aggregation of hSOD1. Here we used the matrix-assisted laser desorption ionization-time of flight mass spectroscopy, high-performance liquid chromatography-electrospray ionization mass spectroscopy, and liquid chromatography mass spectroscopy methods to characterize products. Results show that a peptide region (31-36) of hSOD1 containing the Trp-32 residue (VWGSIK) is oxidatively modified to the N-formylkynurenine (NFK)- and kynurenine (Kyn)-containing peptides (V(NFK)GSIK) and (V(Kyn)GSIK) during HCO3--dependent peroxidase activity of hSOD1. Also, UV photolysis of a cobalt complex that generates authentic CO3.- radical induced a similar product profile from hSOD1. Similar products were obtained using a synthetic peptide with the same amino acid sequence (i.e., VWGSIK). We propose a mechanism involving a tryptophanyl radical for CO3.--induced oxidation of Trp-32 residue (VWGSIK) in hSOD1 to V(NFK)GSIK and V(Kyn)GSIK. (C) 2004 Elsevier Inc. All rights reserved.
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