Protein aging by carboxymethylation of lysines generates sites for divalent metal and redox active copper binding: Relevance to diseases of glycoxidative stress
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
Categorie Soggetti
Biochemistry & Biophysics
Journal title
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
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.