Bromofatty aldehyde derived from bromine exposure and myeloperoxidase and eosinophil peroxidase modify GSH and protein
Bromofatty aldehyde derived from bromine exposure and myeloperoxidase and eosinophil peroxidase modify GSH and protein
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DOI：
10.1194/jlr.m083279
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发表时间：
2018-04-01
影响因子：
6.5
通讯作者：
Ford, David A.
中科院分区：
文献类型：
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作者：
Duerr, Mark A.;Palladino, Elisa N. D.;Ford, David A.
α-氯脂肪醛（α-ClO 2 D）和α-溴脂肪醛（α-BrO 2 D）在活化的嗜中性粒细胞和嗜酸性粒细胞中产生。本研究研究了α-BrdD和α-CldD与GSH和蛋白质半胱氨酰残基的巯基反应的能力。最初的研究表明，2-溴代十六烷醛（2-BrHDA）和2-氯代十六烷醛（2-ClHDA）与GSH反应产生相同的脂肪酸甘油酯-GSH加合物（ADD-GSH）。在合成反应和细胞反应中，与2-ClHDA作为前体相比，2-BrHDA-GSH的产生更稳健。NaBr补充佛波醇肉豆蔻酸酯乙酸酯（PMA）激活的中性粒细胞形成更多的α-Brd-D和β-D-GSH相比，非NaBr补充中性粒细胞。优先产生次溴酸和α-Brd-D的原代人嗜酸性粒细胞在PMA刺激后积累α-Brd-GSH。与暴露于空气中的小鼠相比，暴露于Br-2气体的小鼠肺中的α-BrdD和α-BrdD-GSH水平均升高，并且α-BrdD-GSH的全身血浆水平升高。使用这些醛的点击类似物显示了α-ClODN和α-BrODN与蛋白质硫醇的类似相对反应性。总的来说，这些数据表明，GSH和蛋白质加合物的形成是更大的结果，半胱氨酰残基的亲核攻击α-溴代D相比，这是观察到在原代白细胞和小鼠暴露于溴气体。
alpha-Chlorofatty aldehydes (alpha-ClFALDs) and alpha-bromofatty aldehydes (alpha-BrFALDs) are produced in activated neutrophils and eosinophils. This study investigated the ability of alpha-BrFALD and alpha-ClFALD to react with the thiols of GSH and protein cysteinyl residues. Initial studies showed that 2-bromohexadecanal (2-BrHDA) and 2-chlorohexadecanal (2-ClHDA) react with GSH producing the same fatty aldehyde-GSH adduct (FALD-GSH). In both synthetic and cellular reactions, FALD-GSH production was more robust with 2-BrHDA compared with 2-ClHDA as precursor. NaBr-supplemented phorbol myristate acetate (PMA)-activated neutrophils formed more alpha-BrFALD and FALD-GSH compared with non-NaBr-supplemented neutrophils. Primary human eosinophils, which preferentially produce hypobromous acid and alpha-BrFALD, accumulated FALD-GSH following PMA stimulation. Mice exposed to Br-2 gas had increased levels of both alpha-BrFALD and FALD-GSH in the lungs, as well as elevated systemic plasma levels of FALD-GSH in comparison to mice exposed to air. Similar relative reactivity of alpha-ClFALD and alpha-BrFALD with protein thiols was shown using click analogs of these aldehydes. Collectively, these data demonstrate that GSH and protein adduct formation are much greater as a result of nucleophilic attack of cysteinyl residues on alpha-BrFALD compared with alpha-ClFALD, which was observed in both primary leukocytes and in mice exposed to bromine gas.