3-Hydroxykynurenine and 3-hydroxyanthranilic acid generate hydrogen peroxide and promote alpha-crystallin cross-linking by metal ion reduction

Citation
Le. Goldstein et al., 3-Hydroxykynurenine and 3-hydroxyanthranilic acid generate hydrogen peroxide and promote alpha-crystallin cross-linking by metal ion reduction, BIOCHEM, 39(24), 2000, pp. 7266-7275
Citations number
67
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biochemistry & Biophysics
Journal title
BIOCHEMISTRY
ISSN journal
0006-2960 → ACNP
Volume
39
Issue
24
Year of publication
2000
Pages
7266 - 7275
Database
ISI
SICI code
0006-2960(20000620)39:24<7266:3A3AGH>2.0.ZU;2-0
Abstract
The kynurenine pathway catabolite 3-hydroxykynurenine (3HK) and redox-activ e metals such as copper and iron are implicated in cataractogenesis, Here w e investigate the reaction of kynurenine pathway catabolites with copper an d iron, as well as interactions with the major lenticular structural protei ns, the alpha-crystallins. The o-aminophenol kynurenine catabolites 3HK and 3-hydroxyanthranilic acid (3HAA) reduced Cu(II)>Fe(III) to Cu(I) and Fe(II ), respectively, whereas quinolinic acid and the nonphenolic kynurenine cat abolites kynurenine and anthranilic acid did not reduce either metal. Both 3HK and 3HAA generated superoxide and hydrogen peroxide in a copper-depende nt manner. In addition, 3HK and 3HAA fostered copper-dependent alpha-crysta llin cross-linking. 3HK- or 3HAA-modifed alpha-crystallin showed enhanced r edox activity in comparison to unmodified alpha-crystallin or ascorbate-mod ified alpha-crystallin. These data support the possibility that 3HK and 3HA A may be cofactors in the oxidative damage of proteins, such as alpha-cryst allin, through interactions with redox-active metals and especially copper. These findings may have relevance for understanding cataractogenesis and o ther degenerative conditions in which the kynurenine pathway is activated.