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

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-γ-lyase (CSE), cystathionine- β-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 μM, 48 h treatment) in C2C12-derived myotubes, we investigated the protective potential of exogenous and endogenous sources of H2S, i.e., glucoraphanin (30 μM), L-cysteine (150 μM), and 3-mercaptopyruvate (150 μM). 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, O2− 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.

Targeting Hydrogen Sulfide Modulates Dexamethasone-Induced Muscle Atrophy and Microvascular Rarefaction, through Inhibition of NOX4 and Induction of MGF, M2 Macrophages and Endothelial Progenitors

“…Moreover, a recent published study by Micheli et al [ 53 ] showed in vitro results that are in accordance with the in vivo results we report. They established a Dex-induced sarcopenia in an in vitro model in C2C12-derived myotubes; they studied the role of exogenous and endogenous H2S sources.…”

The Antioxidant Properties of Glucosinolates in Cardiac Cells Are Independent of H2S Signaling

“…H 2 S is an important gasotransmitter with known cardioprotective effects [8][9][10]. H 2 S has been reported to be released from the enzymatic degradation products of some GSLs, i.e., ITCs, in physiological conditions [15,27,28]. This study explored the antioxidant effects of GSLs in cardiac cells and examined the possible utility of H 2 S signaling in mediating the functions of GSLs.…”

Searching for Novel Sources of Hydrogen Sulfide Donors: Chemical Profiling of Polycarpa aurata Extract and Evaluation of the Anti-Inflammatory Effects

“…In this context, natural H 2 S donors existing in plants have shown remarkable biological activity. To date, there is a large body of literature showing the beneficial effect of natural products as H 2 S releasers, such as glucoerucin, glucoraphanin, diallyl trisulfide (DATS), and diallyl disulfide (DADS) occurring in rocket, cruciferous vegetables, or garlic [32][33][34][35][36][37]. Alongside these compounds, many other small natural molecule polysulfides have received attention as equally or more active sources of H 2 S or alternatively viable reservoirs of sulfane sulfur through the transsulfuration pathway [38].…”