Sarcopenia is a gradual and generalized skeletal muscle (SKM) syndrome, characterized by the impairment of muscle components and functionality. Hydrogen sulfide (H2S), endogenously formed within the body from the activity of cystathionine-gamma-lyase (CSE), cystathionine-beta-synthase (CBS), and mercaptopyruvate sulfurtransferase, is involved in SKM function. Here, in an in vitro model of sarcopenia based on damage induced by dexamethasone (DEX, 1 mu M, 48 h treatment) in C2C12-derived myotubes, we investigated the protective potential of exogenous and endogenous sources of H2S, i.e., glucoraphanin (30 mu M), L-cysteine (150 mu M), and 3-mercaptopyruvate (150 mu M). DEX impaired the H2S signalling in terms of a reduction in CBS and CSE expression and H2S biosynthesis. Glucoraphanin and 3-mercaptopyruvate but not L-cysteine prevented the apoptotic process induced by DEX. In parallel, the H2S-releasing molecules reduced the oxidative unbalance evoked by DEX, reducing catalase activity, O-2(-) levels, and protein carbonylation. Glucoraphanin, 3-mercaptopyruvate, and L-cysteine avoided the changes in myotubes morphology and morphometrics after DEX treatment. In conclusion, in an in vitro model of sarcopenia, an impairment in CBS/CSE/H2S signalling occurs, whereas glucoraphanin, a natural H2S-releasing molecule, appears more effective for preventing the SKM damage. Therefore, glucoraphanin supplementation could be an innovative therapeutic approach in the management of sarcopenia.

Beneficial Effect of H2S-Releasing Molecules in an In Vitro Model of Sarcopenia: Relevance of Glucoraphanin / Micheli, Laura; Mitidieri, Emma; Turnaturi, Carlotta; Vanacore, Domenico; Ciampi, Clara; Lucarini, Elena; Cirino, Giuseppe; Ghelardini, Carla; Sorrentino, Raffaella; Di Cesare Mannelli, Lorenzo; d'Emmanuele di Villa Bianca, Roberta. - In: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. - ISSN 1422-0067. - ELETTRONICO. - 23:(2022), pp. 5955-5955. [10.3390/ijms23115955]

Beneficial Effect of H2S-Releasing Molecules in an In Vitro Model of Sarcopenia: Relevance of Glucoraphanin

Micheli, Laura;Ciampi, Clara;Lucarini, Elena;Cirino, Giuseppe;Ghelardini, Carla;Di Cesare Mannelli, Lorenzo
;
2022

Abstract

Sarcopenia is a gradual and generalized skeletal muscle (SKM) syndrome, characterized by the impairment of muscle components and functionality. Hydrogen sulfide (H2S), endogenously formed within the body from the activity of cystathionine-gamma-lyase (CSE), cystathionine-beta-synthase (CBS), and mercaptopyruvate sulfurtransferase, is involved in SKM function. Here, in an in vitro model of sarcopenia based on damage induced by dexamethasone (DEX, 1 mu M, 48 h treatment) in C2C12-derived myotubes, we investigated the protective potential of exogenous and endogenous sources of H2S, i.e., glucoraphanin (30 mu M), L-cysteine (150 mu M), and 3-mercaptopyruvate (150 mu M). DEX impaired the H2S signalling in terms of a reduction in CBS and CSE expression and H2S biosynthesis. Glucoraphanin and 3-mercaptopyruvate but not L-cysteine prevented the apoptotic process induced by DEX. In parallel, the H2S-releasing molecules reduced the oxidative unbalance evoked by DEX, reducing catalase activity, O-2(-) levels, and protein carbonylation. Glucoraphanin, 3-mercaptopyruvate, and L-cysteine avoided the changes in myotubes morphology and morphometrics after DEX treatment. In conclusion, in an in vitro model of sarcopenia, an impairment in CBS/CSE/H2S signalling occurs, whereas glucoraphanin, a natural H2S-releasing molecule, appears more effective for preventing the SKM damage. Therefore, glucoraphanin supplementation could be an innovative therapeutic approach in the management of sarcopenia.
2022
23
5955
5955
Micheli, Laura; Mitidieri, Emma; Turnaturi, Carlotta; Vanacore, Domenico; Ciampi, Clara; Lucarini, Elena; Cirino, Giuseppe; Ghelardini, Carla; Sorrentino, Raffaella; Di Cesare Mannelli, Lorenzo; d'Emmanuele di Villa Bianca, Roberta
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/1295987
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