Rapid cross-linking of proteins by 4-ketoaldehydes and 4-hydroxy-2-alkenals does not arise from the lysine-derived monoalkylpyrroles.
Rapid cross-linking of proteins by 4-ketoaldehydes and 4-hydroxy-2-alkenals does not arise from the lysine-derived monoalkylpyrroles.
复制标题
4-酮醛和 4-羟基-2-烯醛引起的蛋白质快速交联并不是由赖氨酸衍生的单烷基吡咯引起的。
DOI：
10.1021/tx990056a
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发表时间：
1999
影响因子：
4.1
通讯作者：
Sayre,LM
中科院分区：
文献类型：
--
作者：
Xu,G;Liu,Y;Kansal,MM;Sayre,LM
将蛋白质暴露于4-羟基-2-壬烯醛（HNE）导致赖氨酸部分转化为2-戊基吡咯，其可以通过暴露于异构体4-氧代壬醛以更高的产率形成。由于HNE和4-氧代壬醛均引起蛋白质交联，并且由于已知γ-二酮对蛋白质的吡咯化也导致蛋白质交联，因此认为最初形成的2-戊基吡咯负责HNE和4-氧代壬醛所见的蛋白质交联。在这里，我们表明，蛋白质结合的2-烷基吡咯产品与修改4-羟基-2-烯醛和4-氧代烷醛，仅具有单烷基取代，诱导不可检测的水平的自氧化介导的蛋白质交联随着时间的推移，其中父母醛的影响广泛的蛋白质交联，然后必须通过替代机制发生。最后，使用RNA酶和BSA，我们发现赖氨酸的还原甲基化阻断了由HNE或4-氧代壬醛诱导的蛋白质交联（以及在HNE的情况下荧光的发展），这暗示了赖氨酸在交联反应中的强制性作用。
Exposure of proteins to 4-hydroxy-2-nonenal (HNE) results in conversion of lysines in part to 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 proteins by γ-diketones is also known to result in protein cross-linking, it has been considered that the initially formed 2-pentylpyrroles are responsible for the protein cross-linking seen for HNE and 4-oxononanal. Here we show that protein-bound 2-alkylpyrrole products associated with modification by 4-hydroxy-2-alkenals and 4-oxoalkanals, possessing only monoalkyl substitution, induce undetectable levels of autoxidation-mediated protein cross-linking over time periods where the parent aldehydes effect extensive protein cross-linking, which then must be occurring through alternative mechanisms. Finally, using both RNase and BSA, our finding that reductive methylation 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 lysines in the cross-linking reactions.