The effects of nitroxyl (HNO) on H_2O_2 metabolism and possible mechanisms of HNO signaling

摘要

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 H_2O_2. In fact, these classes of proteins not only react with H_2O_2, and thus potentially responsible for the signaling actions of H_2O_2, but are also responsible for the degradation of H_2O_2. Therefore, it is not unreasonable to speculate that HNO can affect H_2O_2 degradation by interacting with H_2O_2-degrading proteins possibly leading to an increase in H_2O_2-mediated signaling. Moreover, considering the commonality between HNO and H _2O_2 biological targets, it also seems likely that HNO-mediated signaling can also be due to reactivity at otherwise H _2O_2-reactive sites. Herein, it is found that HNO does indeed inhibit H_2O_2 degradation via inhibition of H _2O_2-metaboilizing proteins. Also, it is found that in a system known to be regulated by H_2O_2 (T cell activation), HNO behaves similarly to H_2O_2, indicating that HNO- and H_2O_2-signaling may be similar and/or intimately related.