Protein aging by carboxymethylation of lysines generates sites for divalent metal and redox active copper binding: Relevance to diseases of glycoxidative stress

Citation
Ak. Saxena et al., Protein aging by carboxymethylation of lysines generates sites for divalent metal and redox active copper binding: Relevance to diseases of glycoxidative stress, BIOC BIOP R, 260(2), 1999, pp. 332-338
Citations number
51
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biochemistry & Biophysics
Journal title
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
ISSN journal
0006-291X → ACNP
Volume
260
Issue
2
Year of publication
1999
Pages
332 - 338
Database
ISI
SICI code
0006-291X(19990705)260:2<332:PABCOL>2.0.ZU;2-H
Abstract
Aging and age-related diseases are associated with the production of reacti ve oxygen species which modify lipids, proteins and DNA, Here we hypothesiz ed the glyco- and lipoxidation product N-epsilon-(carboxymethyl)lysine (CML ) in proteins should bind divalent and redox active transition metal bindin g, CML-rich poly-L-lysine and bovine serum albumin (BSA) were chemically pr epared and found to bind non-dialyzable Cu2+, Zn2+ and Ca2+. CML-BSA-copper complexes oxidized ascorbate and depolymerized protein in the presence of H2O2. CML-rich tail tendons implanted for 25 days into the peritoneal cavit y of diabetic rats had a 150% increase in copper content and oxidized ascor bate three times faster than controls, CML-rich proteins immunoprecipitated from serum of uremic patients oxidized four times more ascorbate than cont rol and generated spin adducts of DMPO in the presence of H2O2, The chelato r DTPA suppressed ascorbate oxidation thereby implicating transition metals in the process. In aging and disease, CML accumulation may result in a del eterious vicious cycle since CML formation itself is catalyzed by lipoxidat ion and glycoxidation. (C) 1999 Academic Press.