3-Hydroxykynurenine and 3-Hydroxyanthranilic Acid Generate Hydrogen Peroxide and Promote -Crystallin Cross-Linking by Metal Ion Redu
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- 作者：Lee E. Goldstein ; Michael C. Leopold ; Xudong Huang ; Craig S. Atwood ; Aleister J. Saunders ; Mariana Hartshorn ; James T. Lim ; Kyle Y. Faget ; Julien A. Muffat ; Richard C. Scarpa ; Leo T. Chylack ; Jr. ; Edm
- 刊名：Biochemistry
- 出版年：2000
- 出版时间：June 20, 2000
- 年：2000
- 卷：39
- 期：24
- 页码：7266 - 7275
- 全文大小：154K
- 年卷期：v.39,no.24(June 20, 2000)
- ISSN：1520-4995
文摘
The kynurenine pathway catabolite 3-hydroxykynurenine (3HK) and redox-active metals suchas copper and iron are implicated in cataractogenesis. Here we investigate the reaction of kynureninepathway catabolites with copper and iron, as well as interactions with the major lenticular structural proteins,the 
-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 nonphenolickynurenine catabolites kynurenine and anthranilic acid did not reduce either metal. Both 3HK and 3HAAgenerated superoxide and hydrogen peroxide in a copper-dependent manner. In addition, 3HK and 3HAAfostered copper-dependent -crystallin cross-linking. 3HK- or 3HAA-modifed -crystallin showed enhancedredox activity in comparison to unmodified -crystallin or ascorbate-modified -crystallin. These datasupport the possibility that 3HK and 3HAA may be cofactors in the oxidative damage of proteins, suchas -crystallin, through interactions with redox-active metals and especially copper. These findings mayhave relevance for understanding cataractogenesis and other degenerative conditions in which the kynureninepathway is activated.
-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 nonphenolickynurenine catabolites kynurenine and anthranilic acid did not reduce either metal. Both 3HK and 3HAAgenerated superoxide and hydrogen peroxide in a copper-dependent manner. In addition, 3HK and 3HAAfostered copper-dependent -crystallin cross-linking. 3HK- or 3HAA-modifed -crystallin showed enhancedredox activity in comparison to unmodified -crystallin or ascorbate-modified -crystallin. These datasupport the possibility that 3HK and 3HAA may be cofactors in the oxidative damage of proteins, suchas -crystallin, through interactions with redox-active metals and especially copper. These findings mayhave relevance for understanding cataractogenesis and other degenerative conditions in which the kynureninepathway is activated.