Abstract
Aims Insulin and glucocorticoids play crucial roles in skeletal muscle protein turnover. Fast-twitch glycolytic fibres are more susceptible to atrophy than slow-twitch oxidative fibres. Based on accumulating evidence, hydrogen sulfide (H2S) is a physiological mediator of this process. The regulatory effect of H2S on protein synthesis in fast-twitch fibres was evaluated. Results A NaHS (sodium hydrosulfide) injection simultaneously increased the diameter of M. pectoralis major (i.e., fast-twitch glycolytic fibres) and activated the mammalian target of the rapamycin (mTOR)/p70S6 kinase (p70S6K) pathway. Dexamethasone (DEX) inhibited protein synthesis, downregulated mTOR and p70S6K phosphorylation, and suppressed the expression of the cystathionine γ-lyase (CSE) protein in myoblasts. The precursor of H2S, L-cysteine, completely abolished the inhibitory effects of DEX. The CSE inhibitor DL-propargylglycine (PAG) completely abrogated the effects of RU486 on blocking the suppressive effects of DEX. The H2S donor NaHS increased the H2S concentrations and abrogated the inhibitory effects of DEX on protein synthesis. Insulin increased protein synthesis and upregulated CSE expression. However, PAG abrogated the stimulatory effects of insulin on protein synthesis and the activity of the mTOR/p70S6K pathway. Innovation These results demonstrated that CSE/H2S regulated protein synthesis in fast-twitch muscle fibres, and glucocorticoids and insulin regulated protein synthesis in an endogenous CSE/H2S system-dependent manner. Conclusions The results from the present study suggest that the endogenous CSE/H2S system regulates fast-twitch glycolytic muscle degeneration and regeneration.
Highlights
Hydrogen sulfide (H2S) has historically been considered a toxic environmental gas [1] but is a physiological mediator [2,3,4]
Human skeletal muscles express significant amounts of CBS and cystathionine γ-lyase (CSE) [17], suggesting that endogenous H2S plays an important role in modulating muscle metabolism
We investigated the role of H2S in the regulatory effects of glucocorticoids and insulin on myocyte protein synthesis
Summary
Hydrogen sulfide (H2S) has historically been considered a toxic environmental gas [1] but is a physiological mediator [2,3,4]. Hydrogen sulfide plays various physiological roles in neuromodulation, vascular tone regulation, cytoprotection, oxygen-sensing capacity, inflammatory regulation, and cell growth [9,10,11]. The sulfur-containing amino acids, cysteine and homocysteine, are substrates in reactions that produce H2S [13, 14]. 3-Mercaptopyruvate sulfur transferase produces H2S in the vascular endothelium [15], and the sulfur-containing amino acids, methionine, homocysteine, cysteine (CS), and 3-mercaptopyruvate, are the primary sources of endogenous H2S [13, 16]. Human skeletal muscles express significant amounts of CBS and CSE [17], suggesting that endogenous H2S plays an important role in modulating muscle metabolism. Hydrogen sulfide is endogenously generated in rat skeletal muscle and protects against oxidative stress by acting as an antioxidant [18]. Researchers have not clearly determined whether H2S exerts antihypertensive, anti-inflammatory, and antioxidant effects on healthy skeletal muscle and on skeletal muscle affected by metabolic syndromes [20]
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