title: The effects of nitroxyl (HNO) on H₂O₂ metabolism and possible mechanisms of HNO signaling.
abstract: 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.
authors.affiliation: Interdepartmental Program in Molecular Toxicology, UCLA School of Public Health, Los Angeles, CA 90095, USA. Electronic address: matthew.jackson@ars.usda.gov.
authors.forename: Matthew I
authors.initials: MI
authors.lastname: Jackson
authors.forename: Hannah F
authors.initials: HF
authors.lastname: Fields
authors.forename: Timothy S
authors.initials: TS
authors.lastname: Lujan
authors.forename: Megan M
authors.initials: MM
authors.lastname: Cantrell
authors.forename: Joseph
authors.initials: J
authors.lastname: Lin
authors.forename: Jon M
authors.initials: JM
authors.lastname: Fukuto
mesh_terms: D000818:Animals; D002374:Catalase / Q000378:metabolism; D002460:Cell Line; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D017353:Gene Deletion; D005979:Glutathione Peroxidase / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D019169:Jurkat Cells; D017493:Leukocyte Common Antigens / Q000378:metabolism; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000235:genetics; D051379:Mice; D009589:Nitrogen Oxides / Q000378:metabolism*; D010084:Oxidation-Reduction; D010766:Phosphorylation; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000378:metabolism*
chemical_list: D009589:Nitrogen Oxides; D006861:Hydrogen Peroxide; D002374:Catalase; D005979:Glutathione Peroxidase; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D048049:Extracellular Signal-Regulated MAP Kinases; D017493:Leukocyte Common Antigens; C039900:nitroxyl
keywords: CD45; Hydrogen peroxide; Jurkat cells; Nitroxyl; Redox signaling; T cell activation; Thiol proteins