The role of reactive N-bromo species and radical intermediates in hypobromous acid-induced protein oxidation
The role of reactive N-bromo species and radical intermediates in hypobromous acid-induced protein oxidation
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DOI：
10.1016/j.freeradbiomed.2005.05.011
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发表时间：
2005-10-01
影响因子：
7.4
通讯作者：
Davies, MJ
中科院分区：
文献类型：
--
作者：
Hawkins, CL;Davies, MJ
活化的嗜酸性粒细胞和由这些细胞产生的次溴酸（HOBr）与哮喘、过敏反应和某些感染中的组织损伤有关。蛋白质是这种氧化剂的主要目标，但有限的信息是可用的损伤和形成的中间体的机制。HOW与蛋白质的反应显示导致从侧链和主链胺和酰胺形成溴代马胺和溴代酰胺，以及从Tyr残基形成3-溴-和3，5-二溴-Tyr;这些材料占约10%。消耗了70%的氧化剂。蛋白质羰基、二酪氨酸和3，4-二羟基苯丙氨酸也会形成，尽管这些都是次要产物（添加的HOBr < 5%）。对于BSA，还观察到广泛的（选择性和非特异性）蛋白质片段化和有限的聚集。溴胺/溴酰胺是不稳定的，并诱导进一步的氧化和自由基形成，如通过EPR自旋捕获检测到的。获得了在氨基酸、肽和蛋白质的侧链和主链酰胺基团上产生以氮为中心的自由基的证据。这些自由基容易发生重排反应，得到碳中心自由基。对于蛋白质，检测到α-碳（骨架）自由基，其可能在蛋白质片段化中起作用。还观察到一种新的损伤转移途径，从谷氨酰胺侧链的酰胺基团的骨干网站。(c)2005年爱思唯尔公司All rights reserved.
Activated eosinophils, and hypobromous acid (HOBr) generated by these cells, have been implicated in the tissue injury in asthma, allergic reactions, and some infections. Proteins are major targets for this oxidant, but limited information is available on the mechanisms of damage and intermediates formed. Reaction of HOW with proteins is shown to result in the formation of bromarnines and bromamides, from side-chain and backbone amines and amides, and 3-bromo- and 3,5-dibromo-Tyr, from Tyr residues; these materials account for ca. 70% of the oxidant consumed. Protein carbonyls, dityrosine, and 3,4-dihydroxyphenylalanine are also formed, though these are minor products (< 5% of HOBr added). With BSA, extensive (selective and nonspecific) protein fragmentation and limited aggregation are also observed. The bromamines/bromamides are unstable and induce further oxidation and free radical formation as detected by EPR spin trapping. Evidence was obtained for the generation of nitrogen-centered radicals on side-chain and backbone amide groups of amino acids, peptides, and proteins. These radicals readily undergo rearrangement reactions to give carbon-centered radicals. With proteins, a-carbon (backbone) radicals are detected, which may play a role in protein fragmentation. A novel damage transfer pathway from Gln side-chain amide groups to backbone sites was also observed. (c) 2005 Elsevier Inc. All rights reserved.