Biochemical and cellular effects of electrophiles present in ambient air samples
Biochemical and cellular effects of electrophiles present in ambient air samples
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DOI：
10.1016/j.atmosenv.2010.01.045
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发表时间：
2010-04-01
影响因子：
5
通讯作者：
Shinyashiki, Masaru
中科院分区：
文献类型：
--
作者：
Iwamoto, Noriko;Nishiyama, Akira;Shinyashiki, Masaru
在加州的滨江采集的环境气相样品表明，氧化还原和亲电活性都存在，气相中亲电物质的含量高于颗粒相。在这项研究中，使用纯化的巯基蛋白，甘油醛-3-磷酸脱氢酶（GAPDH），蛋白酪氨酸磷酸酶1B（PTP 1B）和KELCH-1样ECH相关蛋白1（Keap 1）的气相亲电试剂的生化效应进行了研究。结果表明，巯基蛋白通过共价修饰被气相样品灭活。接下来，分别在A549和RAW 264.7细胞系中评估两种细胞反应，表皮生长因子受体（EGFR）/促分裂原活化蛋白（MAP）激酶和NF-E2相关因子2（Nrf 2）对环境气相样品的反应。气相样品，在非氧化浓度，增加EGFR的磷酸化，这是负调控的PTP 1B，其下游MAP激酶，细胞外信号调节激酶（ERK）1/2。还观察到需要Keap 1烷基化的Nrf 2的激活及其下游蛋白的表达。环境气相中存在的亲电化合物显示通过共价修饰修饰细胞蛋白质，并激活可导致炎症和适应性反应的多种细胞反应。(c)2010爱思唯尔有限公司版权所有。
Ambient vapor-phase samples collected in Riverside, California had shown that both redox and electrophilic activity were present, with the vapor phase containing higher levels of electrophiles than the particle phase. In this study, the biochemical effects of the vapor-phase electrophiles were examined using the purified thiol proteins, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), protein tyrosine phosphatase 1B (PTP1B) and KELCH-1 like ECH-associated protein 1 (Keap1). The results demonstrated that the thiol proteins were inactivated by the vapor-phase samples through covalent modifications. Next, two cellular responses, epidermal growth factor receptor (EGFR)/mitogen-activated protein (MAP) kinase and NF-E2-related factor 2 (Nrf2), to the ambient vapor-phase samples were assessed in A549 and RAW 264.7 cell lines, respectively. The vapor-phase samples, at non-oxidative concentrations, increased phosphorylation of EGFR, which is negatively regulated by PTP1B, and its downstream MAP kinase, extracellular signal-regulated kinase (ERK)1/2. Activation of Nrf2, which requires Keap1 alkylation, and expression of its downstream proteins were also observed. The electrophilic compounds present in ambient vapor-phase were shown to modify cellular proteins through covalent modification and to activate diverse cellular responses that can lead to inflammatory and adaptive responses. (c) 2010 Elsevier Ltd. All rights reserved.