Rapid Cross-Linking of Proteins by 4-Ketoaldehydes and 4-Hydroxy-2-alkenals Does Not Arise from the Lysine-Derived Monoalkylpyrroles
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- 作者：Guozhang Xu ; Yahua Liu ; Mayank M. Kansal ; and Lawrence M. Sayre
- 刊名：Chemical Research in Toxicology
- 出版年：1999
- 出版时间：September 1999
- 年：1999
- 卷：12
- 期：9
- 页码：855 - 861
- 全文大小：172K
- 年卷期：v.12,no.9(September 1999)
- ISSN：1520-5010
文摘
Exposure of proteins to 4-hydroxy-2-nonenal (HNE) results in conversion of lysines in partto 2-pentylpyrroles that can be formed in higher yield by exposure to the isomeric 4-oxononanal.Since both HNE and 4-oxononanal cause protein cross-linking, and since pyrrolation of proteinsby 
-diketones is also known to result in protein cross-linking, it has been considered that theinitially formed 2-pentylpyrroles are responsible for the protein cross-linking seen for HNEand 4-oxononanal. Here we show that protein-bound 2-alkylpyrrole products associated withmodification by 4-hydroxy-2-alkenals and 4-oxoalkanals, possessing only monoalkyl substitution, induce undetectable levels of autoxidation-mediated protein cross-linking over time periodswhere the parent aldehydes effect extensive protein cross-linking, which then must be occurringthrough alternative mechanisms. Finally, using both RNase and BSA, our finding that reductivemethylation of lysines blocks protein cross-linking induced by either HNE or 4-oxononanal(and development of fluorescence in the case of HNE) implicates the obligatory role of lysinesin the cross-linking reactions.
-diketones is also known to result in protein cross-linking, it has been considered that theinitially formed 2-pentylpyrroles are responsible for the protein cross-linking seen for HNEand 4-oxononanal. Here we show that protein-bound 2-alkylpyrrole products associated withmodification by 4-hydroxy-2-alkenals and 4-oxoalkanals, possessing only monoalkyl substitution, induce undetectable levels of autoxidation-mediated protein cross-linking over time periodswhere the parent aldehydes effect extensive protein cross-linking, which then must be occurringthrough alternative mechanisms. Finally, using both RNase and BSA, our finding that reductivemethylation of lysines blocks protein cross-linking induced by either HNE or 4-oxononanal(and development of fluorescence in the case of HNE) implicates the obligatory role of lysinesin the cross-linking reactions.