Chemical Characterization of the Smallest S-Nitrosothiol, HSNO; Cellular Cross-talk of H₂S and S-Nitrosothiols
Dihydrogen sulfide recently emerged as a biological signaling molecule with important physiological roles and significant pharmacological potential. Chemically plausible explanations for its mechanisms of action have remained elusive, however. Here, we report that H2S reacts with S-nitrosothiols to...
| Main Authors: | , , , , , , , , |
|---|---|
| Other Authors: | |
| Format: | Article |
| Language: | en_US |
| Published: |
American Chemical Society
2013
|
| Online Access: | http://hdl.handle.net/1721.1/79076 https://orcid.org/0000-0002-2693-4982 |
| _version_ | 1826210529950040064 |
|---|---|
| author | Filipovic, Milos R. Miljkovic, Jan Lj. Nauser, Thomas Royzen, Maksim Klos, Katharina Shubina, Tatyana Koppenol, Willem H. Lippard, Stephen J. Ivanović-Burmazović, Ivana |
| author2 | Massachusetts Institute of Technology. Department of Chemistry |
| author_facet | Massachusetts Institute of Technology. Department of Chemistry Filipovic, Milos R. Miljkovic, Jan Lj. Nauser, Thomas Royzen, Maksim Klos, Katharina Shubina, Tatyana Koppenol, Willem H. Lippard, Stephen J. Ivanović-Burmazović, Ivana |
| author_sort | Filipovic, Milos R. |
| collection | MIT |
| description | Dihydrogen sulfide recently emerged as a biological signaling molecule with important physiological roles and significant pharmacological potential. Chemically plausible explanations for its mechanisms of action have remained elusive, however. Here, we report that H2S reacts with S-nitrosothiols to form thionitrous acid (HSNO), the smallest S-nitrosothiol. These results demonstrate that, at the cellular level, HSNO can be metabolized to afford NO+, NO, and NO– species, all of which have distinct physiological consequences of their own. We further show that HSNO can freely diffuse through membranes, facilitating transnitrosation of proteins such as hemoglobin. The data presented in this study explain some of the physiological effects ascribed to H2S, but, more broadly, introduce a new signaling molecule, HSNO, and suggest that it may play a key role in cellular redox regulation. |
| first_indexed | 2024-09-23T14:51:25Z |
| format | Article |
| id | mit-1721.1/79076 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T14:51:25Z |
| publishDate | 2013 |
| publisher | American Chemical Society |
| record_format | dspace |
| spelling | mit-1721.1/790762022-10-01T22:56:46Z Chemical Characterization of the Smallest S-Nitrosothiol, HSNO; Cellular Cross-talk of H₂S and S-Nitrosothiols Filipovic, Milos R. Miljkovic, Jan Lj. Nauser, Thomas Royzen, Maksim Klos, Katharina Shubina, Tatyana Koppenol, Willem H. Lippard, Stephen J. Ivanović-Burmazović, Ivana Massachusetts Institute of Technology. Department of Chemistry Lippard, Stephen J. Royzen, Maksim Dihydrogen sulfide recently emerged as a biological signaling molecule with important physiological roles and significant pharmacological potential. Chemically plausible explanations for its mechanisms of action have remained elusive, however. Here, we report that H2S reacts with S-nitrosothiols to form thionitrous acid (HSNO), the smallest S-nitrosothiol. These results demonstrate that, at the cellular level, HSNO can be metabolized to afford NO+, NO, and NO– species, all of which have distinct physiological consequences of their own. We further show that HSNO can freely diffuse through membranes, facilitating transnitrosation of proteins such as hemoglobin. The data presented in this study explain some of the physiological effects ascribed to H2S, but, more broadly, introduce a new signaling molecule, HSNO, and suggest that it may play a key role in cellular redox regulation. Friedrich-Alexander-Universität Erlangen-Nürnberg (Intermural grant from Emerging Field Initiative: Medicinal Redox Inorganic Chemistry) National Science Foundation (U.S.) National Institutes of Health (U.S.) (Postdoctoral Fellowship) 2013-06-06T20:17:11Z 2013-06-06T20:17:11Z 2012-07 2012-01 Article http://purl.org/eprint/type/JournalArticle 0002-7863 1520-5126 http://hdl.handle.net/1721.1/79076 Filipovic, Milos R., Jan Lj. Miljkovic, Thomas Nauser, et al. 2012Chemical Characterization of the Smallest S -Nitrosothiol, HSNO; Cellular Cross-talk of H₂S and S -Nitrosothiols. Journal of the American Chemical Society 134(29): 12016–12027. https://orcid.org/0000-0002-2693-4982 en_US http://dx.doi.org/10.1021/ja3009693 Journal of the American Chemical Society Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf American Chemical Society American Chemical Society |
| spellingShingle | Filipovic, Milos R. Miljkovic, Jan Lj. Nauser, Thomas Royzen, Maksim Klos, Katharina Shubina, Tatyana Koppenol, Willem H. Lippard, Stephen J. Ivanović-Burmazović, Ivana Chemical Characterization of the Smallest S-Nitrosothiol, HSNO; Cellular Cross-talk of H₂S and S-Nitrosothiols |
| title | Chemical Characterization of the Smallest S-Nitrosothiol, HSNO; Cellular Cross-talk of H₂S and S-Nitrosothiols |
| title_full | Chemical Characterization of the Smallest S-Nitrosothiol, HSNO; Cellular Cross-talk of H₂S and S-Nitrosothiols |
| title_fullStr | Chemical Characterization of the Smallest S-Nitrosothiol, HSNO; Cellular Cross-talk of H₂S and S-Nitrosothiols |
| title_full_unstemmed | Chemical Characterization of the Smallest S-Nitrosothiol, HSNO; Cellular Cross-talk of H₂S and S-Nitrosothiols |
| title_short | Chemical Characterization of the Smallest S-Nitrosothiol, HSNO; Cellular Cross-talk of H₂S and S-Nitrosothiols |
| title_sort | chemical characterization of the smallest s nitrosothiol hsno cellular cross talk of h₂s and s nitrosothiols |
| url | http://hdl.handle.net/1721.1/79076 https://orcid.org/0000-0002-2693-4982 |
| work_keys_str_mv | AT filipovicmilosr chemicalcharacterizationofthesmallestsnitrosothiolhsnocellularcrosstalkofh2sandsnitrosothiols AT miljkovicjanlj chemicalcharacterizationofthesmallestsnitrosothiolhsnocellularcrosstalkofh2sandsnitrosothiols AT nauserthomas chemicalcharacterizationofthesmallestsnitrosothiolhsnocellularcrosstalkofh2sandsnitrosothiols AT royzenmaksim chemicalcharacterizationofthesmallestsnitrosothiolhsnocellularcrosstalkofh2sandsnitrosothiols AT kloskatharina chemicalcharacterizationofthesmallestsnitrosothiolhsnocellularcrosstalkofh2sandsnitrosothiols AT shubinatatyana chemicalcharacterizationofthesmallestsnitrosothiolhsnocellularcrosstalkofh2sandsnitrosothiols AT koppenolwillemh chemicalcharacterizationofthesmallestsnitrosothiolhsnocellularcrosstalkofh2sandsnitrosothiols AT lippardstephenj chemicalcharacterizationofthesmallestsnitrosothiolhsnocellularcrosstalkofh2sandsnitrosothiols AT ivanovicburmazovicivana chemicalcharacterizationofthesmallestsnitrosothiolhsnocellularcrosstalkofh2sandsnitrosothiols |