Serum electrolytes can promote hydroxyl radical-initiated biomolecular damage from inflammation
Serum electrolytes can promote hydroxyl radical-initiated biomolecular damage from inflammation
复制标题
DOI：
10.1016/j.freeradbiomed.2019.07.023
复制
发表时间：
2019-09-01
影响因子：
7.4
通讯作者：
Mitch, William A.
中科院分区：
文献类型：
--
作者：
Komaki, Yukako;Simpson, Adam M-A;Mitch, William A.
慢性炎症性疾病与生物分子损伤有关，部分归因于与活性氧（ROS）的反应，特别是羟基自由基（(OH)- o -中心点）。然而，血清电解质对ros相关损伤的影响很少受到关注。我们证明(OH)- o -中心点通过与血清相关的碳酸盐和卤化物浓度的反应转化为碳酸盐和卤素自由基，从根本上改变了氨基酸的靶向性和过氧化氢酶、白蛋白和碳酸酐酶（三种重要的血液蛋白）酶活性的丧失。化学动力学模型表明，碳酸盐和卤素自由基浓度应分别超过(OH)- o中心点浓度6和2个数量级。稳态γ -辐射分解实验表明，血清水平的碳酸盐和卤化物使酪氨酸、色氨酸和过氧化氢酶的酶活性损失增加了6倍。这些结果是针对碳酸盐和卤化物的，而不是一般的离子强度效应。血清碳酸盐和卤化物增加了白蛋白中酪氨酸和蛋氨酸的降解，增加了组氨酸的降解，同时降低了碳酸酐酶的酶活性损失。血清电解质增加了酪氨酸、色氨酸的降解和模型酶酮类固醇异构酶的酶活性，主要是由于碳酸盐自由基反应。对突变型酮类固醇异构酶的处理表明，优先靶向活性位点酪氨酸占总酪氨酸损失的一半。结果表明，碳酸盐和卤素自由基可能比(OH)- o中心点对血清中蛋白质降解的驱动作用更显著。解释这些子自由基对生物分子的选择性靶向作用，对于理解氧化应激的后果具有重要意义。
Chronic inflammatory disorders are associated with biomolecular damage attributed partly to reactions with Reactive Oxygen Species (ROS), particularly hydroxyl radicals ((OH)-O-center dot). However, the impacts of serum electrolytes on ROS-associated damage has received little attention. We demonstrate that the conversion of (OH)-O-center dot to carbonate and halogen radicals via reactions with serum-relevant carbonate and halide concentrations fundamentally alters the targeting of amino acids and loss of enzymatic activity in catalase, albumin and carbonic anhydrase, three important blood proteins. Chemical kinetic modeling indicated that carbonate and halogen radical concentrations should exceed (OH)-O-center dot concentrations by 6 and 2 orders of magnitude, respectively. Steady-state gamma-radiolysis experiments demonstrated that serum-level carbonates and halides increased tyrosine, tryptophan and enzymatic activity losses in catalase up to 6-fold. These outcomes were specific to carbonates and halides, not general ionic strength effects. Serum carbonates and halides increased the degradation of tyrosines and methionines in albumin, and increased the degradation of histidines while decreasing enzymatic activity loss in carbonic anhydrase. Serum electrolytes increased the degradation of tyrosines, tryptophans and enzymatic activity in the model enzyme, ketosteroid isomerase, predominantly due to carbonate radical reactions. Treatment of a mutant ketosteroid isomerase indicated that preferential targeting of the active site tyrosine accounted for half of the total tyrosine loss. The results suggest that carbonate and halogen radicals may be more significant than (OH)-O-center dot as drivers for protein degradation in serum. Accounting for the selective targeting of biomolecules by these daughter radicals is important for developing a mechanistic understanding of the consequences of oxidative stress.