Metal-Catalyzed Oxidation of Protein-Bound Dopamine

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• 作者：Mitsugu Akagawa ; Yoshihisa Ishii ; Takeshi Ishii ; Takahiro Shibata ; Mari Yotsu-Yamashita ; Kyozo Suyama ; Koji Uchida
• 刊名：Biochemistry
• 出版年：2006
• 出版时间：December 19, 2006
• 年：2006
• 卷：45
• 期：50
• 页码：15120 - 15128
• 全文大小：448K
• 年卷期：v.45,no.50(December 19, 2006)
• ISSN：1520-4995

文摘

Dopamine (DA) is an unstable neurotransmitter that readily oxidizes to the DA quinone andforms reactive oxygen species, such as superoxide and hydrogen peroxide. The oxidized dopamine alsoforms thiol conjugates with sulfhydryl groups on cysteine, glutathione, and proteins. In the present study,we determined the redox potential of the protein-bound DA and established a novel mechanism for theoxidative modification of the protein, in which the DA-cysteine adduct generated in the DA-modifiedprotein causes oxidative modification of the DA-bound protein in the presence of Cu²⁺. Exposure of asulfhydryl enzyme, glyceraldehyde-3-phosphate dehydrogenase, to DA resulted in a significant loss ofsulfhydryl groups and the formation of the DA-cysteine adduct. When the DA-modified protein wasincubated with Cu²⁺, we observed aggregation and degradation of the DA-bound protein and concomitantformation of a protein carbonyl, a marker of an oxidatively modified protein. Furthermore, we analyzedthe carbonyl products generated during the Cu²⁺-catalyzed oxidation of the DA-modified protein andrevealed the production of glutamic and aminoadipic semialdehydes, consisting of the protein carbonylsgenerated. The cysteinyl-DA residue generated in the DA-modified protein was suggested to represent aredox-active adduct, based on the observations that the cysteinyl-DA adduct, 5-S-cysteinyldopamine,produced by the reaction of cysteine with DA, gave rise to the oxidative modification of bovine serumalbumin in the presence of Cu²⁺. These data suggest that the DA-modified protein may be involved inredox alteration under oxidative stress, whereby DA covalently binds to cysteine residues, generating theredox-active cysteinyl-DA adduct that causes the metal-catalyzed oxidation of protein.