The effects of nitroxyl (HNO) on H₂O₂ metabolism and possible mechanisms of HNO signaling.
The effects of nitroxyl (HNO) on H₂O₂ metabolism and possible mechanisms of HNO signaling.
复制标题
硝酰基 (HNO) 对 H–O– 代谢的影响以及 HNO 信号传导的可能机制。
DOI：
10.1016/j.abb.2013.08.008
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发表时间：
2013
影响因子：
3.9
通讯作者：
Fukuto,JonM
中科院分区：
文献类型：
--
作者：
Jackson,MatthewI;Fields,HannahF;Lujan,TimothyS;Cantrell,MeganM;Lin,Joseph;Fukuto,JonM
硝基（Nitroxyl， HNO）具有独特且潜在重要的生物/生理活性，但目前机制尚不明确。先前的研究表明，HNO可能的生物学靶点是硫醇蛋白、氧化金属蛋白（即铁血红素蛋白）和最有可能的硒蛋白。有趣的是，这些是与H2O2相互作用的同一类蛋白质。事实上，这类蛋白质不仅与H2O2发生反应，因此可能负责H2O2的信号传导作用，而且还负责H2O2的降解。因此，我们可以推测HNO通过与h2o2降解蛋白相互作用影响h2o2降解，可能导致h2o2介导的信号通路增加。此外，考虑到HNO和h2o2生物靶点之间的共性，HNO介导的信号传导似乎也可能是由于其他h2o2活性位点的反应性。本研究发现，HNO确实通过抑制h2o2代谢蛋白抑制h2o2降解。此外，研究还发现，在已知受H2O2（T细胞活化）调节的系统中，HNO的行为与H2O2相似，这表明HNO-和H2O2-信号传导可能相似或密切相关。
Nitroxyl (HNO) possesses unique and potentially important biological/physiological activity that is currently mechanistically ill-defined. Previous work has shown that the likely biological targets for HNO are thiol proteins, oxidized metalloproteins (i.e. ferric heme proteins) and, most likely, selenoproteins. Interestingly, these are the same classes of proteins that interact with H2O2. In fact, these classes of proteins not only react with H2O2, and thus potentially responsible for the signaling actions of H2O2, but are also responsible for the degradation of H2O2. Therefore, it is not unreasonable to speculate that HNO can affect H2O2degradation by interacting with H2O2-degrading proteins possibly leading to an increase in H2O2-mediated signaling. Moreover, considering the commonality between HNO and H2O2biological targets, it also seems likely that HNO-mediated signaling can also be due to reactivity at otherwise H2O2-reactive sites. Herein, it is found that HNO does indeed inhibit H2O2degradation via inhibition of H2O2-metaboilizing proteins. Also, it is found that in a system known to be regulated by H2O2(T cell activation), HNO behaves similarly to H2O2, indicating that HNO- and H2O2-signaling may be similar and/or intimately related.