Metal-catalyzed oxidation of 2-alkenals generates genotoxic 4-oxo-2-alkenals during lipid peroxidation.
Metal-catalyzed oxidation of 2-alkenals generates genotoxic 4-oxo-2-alkenals during lipid peroxidation.
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金属催化的 2-烯醛氧化在脂质过氧化过程中产生遗传毒性的 4-oxo-2-烯醛。
DOI：
10.1080/09168451.2016.1191334
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Kawai Y.
中科院分区：
文献类型：
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作者：
Nuka E;Tomono S;Ishisaka A;Kato Y;Miyoshi N;Kawai Y.
脂质过氧化产物与细胞分子（如DNA碱基）反应形成共价加合物，这与衰老和疾病过程有关。由于脂质过氧化是一个复杂的过程，并发生在多个阶段，可能有未知的反应途径。本文采用液相色谱-串联质谱法对2′-脱氧鸟苷（dG）与氧化花生四烯酸的加合物进行了全面分析，发现7-（2-氧代己基）-乙烯基-dG是主要的未鉴定加合物之一。该加合物的形成在dG与2-辛烯醛并且主要与4-氧代-2-辛烯醛（OOE）的反应中再现。我们还发现，其他2-烯醛（具有五个或更多个碳）生成相应的4-氧代-2-烯醛型加合物。重要的是，发现过渡金属增强了2-辛烯醛的C4-位的氧化，导致OOE-dG加合物的形成。这些发现证明了脂质过氧化过程中形成4-氧代-2-烯醛的新途径，并可能提供金属催化遗传毒性的机制。
Lipid peroxidation products react with cellular molecules, such as DNA bases, to form covalent adducts, which are associated with aging and disease processes. Since lipid peroxidation is a complex process and occurs in multiple stages, there might be yet unknown reaction pathways. Here, we analyzed comprehensively 2′-deoxyguanosine (dG) adducts with oxidized arachidonic acid using liquid chromatography–tandem mass spectrometry and found the formation of 7-(2-oxo-hexyl)-etheno-dG as one of the major unidentified adducts. The formation of this adduct was reproduced in the reaction of dG with 2-octenal and predominantly with 4-oxo-2-octenal (OOE). We also found that other 2-alkenals (with five or more carbons) generate corresponding 4-oxo-2-alkenal-type adducts. Importantly, it was found that transition metals enhanced the oxidation of C4-position of 2-octenal, leading to the formation of OOE-dG adduct. These findings demonstrated a new pathway for the formation of 4-oxo-2-alkenals during lipid peroxidation and might provide a mechanism for metal-catalyzed genotoxicity.