The Effects of Nitroxyl (HNO) on H2O2 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 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 H2O2 degradation by interacting with H2O2-degrading proteins possibly leading to an increase in H2O2-mediated signaling. Moreover, considering the commonality between HNO and H2O2 biological 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 H₂O₂ degradation 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.