Characterization of the Inducible and Slow-Releasing Hydrogen Sulfide and Persulfide Donor P*: Insights into Hydrogen Sulfide Signaling
| Autor: | Erwan Galardon, Bernd Mayer, Anita Fischer, Stefan Toegel, Guenter Steiner, Modesta Trummer, Burkhard Kloesch |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Cell signaling Antioxidant Physiology Hydrogen sulfide medicine.medical_treatment Clinical Biochemistry hydrogen sulfide RM1-950 medicine.disease_cause Biochemistry Article 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine medicine oxidative stress Molecular Biology Protein kinase B Heme Polysulfide Superoxide heme oxygenase-1 Cell Biology equipment and supplies Cell biology human chondrocytes osteoarthritis 030104 developmental biology ATDC5 chemistry inflammation 030220 oncology & carcinogenesis polysulfides Therapeutics. Pharmacology Oxidative stress |
| Zdroj: | Antioxidants, Vol 10, Iss 1049, p 1049 (2021) Antioxidants Volume 10 Issue 7 |
| ISSN: | 2076-3921 |
| DOI: | 10.3390/antiox10071049 |
| Popis: | Hydrogen sulfide (H2S) is an important mediator of inflammatory processes. However, controversial findings also exist, and its underlying molecular mechanisms are largely unknown. Recently, the byproducts of H2S, per-/polysulfides, emerged as biological mediators themselves, highlighting the complex chemistry of H2S. In this study, we characterized the biological effects of P*, a slow-releasing H2S and persulfide donor. To differentiate between H2S and polysulfide-derived effects, we decomposed P* into polysulfides. P* was further compared to the commonly used fast-releasing H2S donor sodium hydrogen sulfide (NaHS). The effects on oxidative stress and interleukin-6 (IL-6) expression were assessed in ATDC5 cells using superoxide measurement, qPCR, ELISA, and Western blotting. The findings on IL-6 expression were corroborated in primary chondrocytes from osteoarthritis patients. In ATDC5 cells, P* not only induced the expression of the antioxidant enzyme heme oxygenase-1 via per-/polysulfides, but also induced activation of Akt and p38 MAPK. NaHS and P* significantly impaired menadione-induced superoxide production. P* reduced IL-6 levels in both ATDC5 cells and primary chondrocytes dependent on H2S release. Taken together, P* provides a valuable research tool for the investigation of H2S and per-/polysulfide signaling. These data demonstrate the importance of not only H2S, but also per-/polysulfides as bioactive signaling molecules with potent anti-inflammatory and, in particular, antioxidant properties. |
| Databáze: | OpenAIRE |
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