Increased hydrogen sulfide turnover serves a cytoprotective role during the development of replicative senescence.

Autor: Kieronska-Rudek A; Chair of Pharmacology, Department of Science and Medicine, University of Fribourg, Fribourg, Switzerland; Jagiellonian University, Jagiellonian Centre for Experimental Therapeutics (JCET), Cracow, Poland., Ascencao K; Chair of Pharmacology, Department of Science and Medicine, University of Fribourg, Fribourg, Switzerland., Chlopicki S; Jagiellonian University, Jagiellonian Centre for Experimental Therapeutics (JCET), Cracow, Poland; Jagiellonian University Medical College, Chair of Pharmacology, Faculty of Medicine, Cracow, Poland., Szabo C; Chair of Pharmacology, Department of Science and Medicine, University of Fribourg, Fribourg, Switzerland. Electronic address: csaba.szabo@unifr.ch.
Jazyk: angličtina
Zdroj: Biochemical pharmacology [Biochem Pharmacol] 2024 Dec; Vol. 230 (Pt 2), pp. 116595. Date of Electronic Publication: 2024 Oct 23.
DOI: 10.1016/j.bcp.2024.116595
Abstrakt: The mammalian gasotransmitter hydrogen sulfide (H 2 S) is produced by enzymes such as cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE), 3-mercaptopyruvate sulfurtransferase (3-MST). Prior studies suggest that H 2 S may have cytoprotective and anti-aging effects. This project explores the regulation and role of endogenous H 2 S in a murine model of replicative senescence. H 2 S and polysulfide levels in RAW 264.7 murine macrophages (control cells: passage 5-10; senescent cells: passage 30-40) were measured using fluorescent probes. The expression of H 2 S-related enzymes and the activity of senescence marker beta-galactosidase (SA-β-Gal) were also analyzed. CBS, CSE, and 3-MST were inhibited using selective pharmacological inhibitors. Senescence led to a moderate upregulation of CBS and in a significant increase in CSE and 3-MST. H 2 S degradation enzymes were also elevated in senescence. Inhibition of H 2 S-producing enzymes reduced H 2 S levels but increased polysulfides. Inhibition of H 2 S production during senescence suppressed cell proliferation, and elevated SA-β-Gal and p21 levels. Comparing young and old mice spleens revealed downregulation of CBS and ETHE1 and upregulation of rhodanese and SUOX in older mice. The results demonstrate that increased reactive sulfur turnover occurs in senescent macrophages and that reactive sulfur species support cell proliferation and regulate cellular senescence.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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