Peroxynitrite and hydrogen peroxide elicit similar cellular stress responses mediated by the Ccp1 sensor protein.
Peroxynitrite and hydrogen peroxide elicit similar cellular stress responses mediated by the Ccp1 sensor protein.
复制标题
过氧亚硝酸盐和过氧化氢会引起类似的由 Ccp1 传感器蛋白介导的细胞应激反应。
DOI：
10.1016/j.freeradbiomed.2015.04.010
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发表时间：
2015
影响因子：
7.4
通讯作者：
A. English
中科院分区：
文献类型：
--
作者：
Dorival Martins;Iolie C Bakas;K. McIntosh;A. English
过氧亚硝酸盐[ONOO（H）]是一种与细胞有害作用相关的氧化剂。由于它是一种与过氧化物酶迅速反应的无机过氧化物，因此我们推测细胞可能以类似的方式对ONOO（H）和H2 O2挑战做出反应。我们将酵母细胞暴露于SIN-1，一种良好表征的ONOO（H）发生器，并观察过氧化氢酶和过氧化物氧还蛋白（Prx）活性的刺激。以前，我们报道过，H2 O2刺激增加了野生型细胞和产生高活性突变型H2 O2传感器Ccp 1 W191 F的细胞的这些活性，但在Ccp 1敲除细胞（ccp 1 Δ）中没有。我们发现ccp 1 Δ和ccp 1 W191 F细胞对SIN-1的反应反映了对H2 O2的反应，确定Ccp 1是两种过氧化物的传感器。SIN-1同时释放·NO和O2·−，它们反应形成ONOO（H），但将三种菌株分别暴露于·NO供体（精胺-NONOate）或O2·−发生器（百草枯）主要抑制过氧化氢酶或Prx活性，而NONOate和百草枯共同激发则刺激这些活性。由于Ccp 1似乎在细胞中感知ONOO（H），我们在体外检测了它与ONOO（H）的反应，发现过氧亚硝酸（ONOOH）迅速（k2> 106 M − 1 s −1）将纯化的Ccp 1氧化成一种中间体，其光谱和铁细胞色素氧化特性与其与H2 O2形成的化合物I的光谱和铁细胞色素氧化特性无法区分。重要的是，从ONOOH释放的亚硝酸盐不会被Ccp 1的化合物I氧化成·NO2，这与参与免疫防御的过氧化物酶不同。总体而言，我们的结果表明酵母细胞对ONOO（H）和H2 O2产生共同的抗氧化反应，其中Ccp 1作为无机过氧化物传感器发挥着关键作用。
Peroxynitrite [ONOO(H)] is an oxidant associated with deleterious effects in cells. Because it is an inorganic peroxide that reacts rapidly with peroxidases, we speculated that cells may respond to ONOO(H) and H2O2challenge in a similar manner. We exposed yeast cells to SIN-1, a well-characterized ONOO(H) generator, and observed stimulation of catalase and peroxiredoxin (Prx) activities. Previously, we reported that H2O2challenge increases these activities in wild-type cells and in cells producing the hyperactive mutant H2O2sensor Ccp1W191Fbut not in Ccp1-knockout cells (ccp1Δ). We find here that the response ofccp1Δ andccp1W191Fcells to SIN-1 mirrors that to H2O2, identifying Ccp1 as a sensor of both peroxides. SIN-1 simultaneously releases•NO and O2•−, which react to form ONOO(H), but exposure of the three strains separately to an•NO donor (spermine-NONOate) or an O2•−generator (paraquat) mainly depresses catalase or Prx activity, whereas co-challenge with the NONOate and paraquat stimulates these activities. Because Ccp1 appears to sense ONOO(H) in cells, we examined its reaction with ONOO(H) in vitro and found that peroxynitrous acid (ONOOH) rapidly (k2>106M−1s−1) oxidizes purified Ccp1 to an intermediate with spectral and ferrocytochrome-oxidizing properties indistinguishable from those of its well-characterized compound I formed with H2O2. Importantly, the nitrite released from ONOOH is not oxidized to•NO2by Ccp1׳s compound I, unlike peroxidases involved in immune defense. Overall, our results reveal that yeast cells mount a common antioxidant response to ONOO(H) and H2O2, with Ccp1 playing a pivotal role as an inorganic peroxide sensor.
影响因子：
2.9
作者：
Han, D;Canali, R;Cadenas, E
通讯作者：
Cadenas, E
影响因子：
2.9
作者：
ERMAN, JE;VITELLO, LB;KRAUT, J
通讯作者：
KRAUT, J
影响因子：
2.9
作者：
Forman, Henry Jay;Maiorino, Matilde;Ursini, Fulvio
通讯作者：
Ursini, Fulvio