Human Cystathionine γ-Lyase Is Inhibited by s-Nitrosation: A New Crosstalk Mechanism between NO and H2S
| Autor: | Alexandra M. M. Antunes, Catarina S. Tomé, Dalila G. F. Fernandes, João B. Vicente, João P. Nunes, Karim Zuhra, Alessandro Giuffrè, João M. F. Costa |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
gasotransmitters
Physiology Clinical Biochemistry hydrogen sulfide Transsulfuration RM1-950 Biochemistry Article Nitric oxide crosstalk S-Nitrosoglutathione chemistry.chemical_compound Signal-ing Molecular Biology Gasotransmitters cystathionine γ-lyase s-nitrosoglutathione Cystathionine ?-lyase biology Chemistry Cell Biology Cystathionine beta synthase Second messenger system biology.protein Therapeutics. Pharmacology Signal transduction signaling Cysteine |
| Zdroj: | Antioxidants Volume 10 Issue 9 Antioxidants, Vol 10, Iss 1391, p 1391 (2021) Antioxidants 10 (2021): 1391. doi:10.3390/antiox10091391 info:cnr-pdr/source/autori:Fernandes, Dalila G.F.; Nunes, João; Tomé, Catarina S.; Zuhra, Karim; Costa, João M.F.; Antunes, Alexandra M.M.; Giuffrè, Alessandro; Vicente, João B./titolo:Human cystathionine gamma-lyase is inhibited by S-nitrosation: A new crosstalk mechanism between NO and H2S/doi:10.3390%2Fantiox10091391/rivista:Antioxidants/anno:2021/pagina_da:1391/pagina_a:/intervallo_pagine:1391/volume:10 |
| ISSN: | 2076-3921 |
| DOI: | 10.3390/antiox10091391 |
| Popis: | The ‘gasotransmitters’ hydrogen sulfide (H2S), nitric oxide (NO), and carbon monoxide (CO) act as second messengers in human physiology, mediating signal transduction via interaction with or chemical modification of protein targets, thereby regulating processes such as neurotransmission, blood flow, immunomodulation, or energy metabolism. Due to their broad reactivity and potential toxicity, the biosynthesis and breakdown of H2S, NO, and CO are tightly regulated. Growing evidence highlights the active role of gasotransmitters in their mutual cross-regulation. In human physiology, the transsulfuration enzymes cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE) are prominent H2S enzymatic sources. While CBS is known to be inhibited by NO and CO, little is known about CSE regulation by gasotransmitters. Herein, we investigated the effect of s-nitrosation on CSE catalytic activity. H2S production by recombinant human CSE was found to be inhibited by the physiological nitrosating agent s-nitrosoglutathione (GSNO), while reduced glutathione had no effect. GSNO-induced inhibition was partially reverted by ascorbate and accompanied by the disappearance of one solvent accessible protein thiol. By combining differential derivatization procedures and mass spectrometry-based analysis with functional assays, seven out of the ten protein cysteine residues, namely Cys84, Cys109, Cys137, Cys172, Cys229, Cys307, and Cys310, were identified as targets of s-nitrosation. By generating conservative Cys-to-Ser variants of the identified s-nitrosated cysteines, Cys137 was identified as most significantly contributing to the GSNO-mediated CSE inhibition. These results highlight a new mechanism of crosstalk between gasotransmitters. |
| Databáze: | OpenAIRE |
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