| Autor: |
Trummer M; Ludwig Boltzmann Institute for Arthritis and Rehabilitation, 1090 Vienna, Austria.; Department of Pharmacology and Toxicology, Institute of Pharmaceutical Sciences, Karl-Franzens-University of Graz, 8010 Graz, Austria., Galardon E; UMR 8601, LCBPT, CNRS-Université de Paris, 75270 Paris, France., Fischer A; Ludwig Boltzmann Institute for Arthritis and Rehabilitation, 1090 Vienna, Austria.; Karl Chiari Lab for Orthopaedic Biology, Department of Orthopedics and Trauma Surgery, Medical University of Vienna, 1090 Vienna, Austria., Toegel S; Ludwig Boltzmann Institute for Arthritis and Rehabilitation, 1090 Vienna, Austria.; Karl Chiari Lab for Orthopaedic Biology, Department of Orthopedics and Trauma Surgery, Medical University of Vienna, 1090 Vienna, Austria., Mayer B; Department of Pharmacology and Toxicology, Institute of Pharmaceutical Sciences, Karl-Franzens-University of Graz, 8010 Graz, Austria., Steiner G; Ludwig Boltzmann Institute for Arthritis and Rehabilitation, 1090 Vienna, Austria.; Division of Rheumatology, Department of Internal Medicine III, Medical University of Vienna, 1090 Vienna, Austria., Kloesch B; Ludwig Boltzmann Institute for Arthritis and Rehabilitation, 1090 Vienna, Austria.; Department of Pharmacology and Toxicology, Institute of Pharmaceutical Sciences, Karl-Franzens-University of Graz, 8010 Graz, Austria. |
| Abstrakt: |
Hydrogen sulfide (H 2 S) is an important mediator of inflammatory processes. However, controversial findings also exist, and its underlying molecular mechanisms are largely unknown. Recently, the byproducts of H 2 S, per-/polysulfides, emerged as biological mediators themselves, highlighting the complex chemistry of H 2 S. In this study, we characterized the biological effects of P*, a slow-releasing H 2 S and persulfide donor. To differentiate between H 2 S and polysulfide-derived effects, we decomposed P* into polysulfides. P* was further compared to the commonly used fast-releasing H 2 S 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 H 2 S release. Taken together, P* provides a valuable research tool for the investigation of H 2 S and per-/polysulfide signaling. These data demonstrate the importance of not only H 2 S, but also per-/polysulfides as bioactive signaling molecules with potent anti-inflammatory and, in particular, antioxidant properties. |
