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Cystathionine gamma‐lyase/H 2 S signaling facilitates myogenesis under aging and injury condition
- Source :
- The FASEB Journal. 35
- Publication Year :
- 2021
- Publisher :
- Wiley, 2021.
-
Abstract
- Hydrogen sulfide (H2 S) can be endogenously produced and belongs to the class of signaling molecules known as gasotransmitters. Cystathionine gamma-lyase (CSE)-derived H2 S is implicated in the regulation of cell differentiation and the aging process, but the involvements of the CSE/H2 S system in myogenesis upon aging and injury have not been explored. In this study, we demonstrated that CSE acts as a major H2 S-generating enzyme in skeletal muscles and is significantly down-regulated in aged skeletal muscles in mice. CSE deficiency exacerbated the age-dependent sarcopenia and cardiotoxin-induced injury/regeneration in mouse skeletal muscle, possibly attributed to inefficient myogenesis. In contrast, supplement of NaHS (an H2 S donor) induced the expressions of myogenic genes and promoted muscle regeneration in mice. In vitro, incubation of myoblast cells (C2C12) with H2 S promoted myogenesis, as evidenced by the inhibition of cell cycle progression and migration, altered expressions of myogenic markers, elongation of myoblasts, and formation of multinucleated myotubes. Myogenesis was also found to upregulate CSE expression, while blockage of CSE/H2 S signaling resulted in a suppression of myogenesis. Mechanically, H2 S significantly induced the heterodimer formation between MEF2c and MRF4 and promoted the binding of MEF2c/MRF4 to myogenin promoter. MEF2c was S-sulfhydrated at both cysteine 361 and 420 in the C-terminal transactivation domain, and blockage of MEF2c S-sulfhydration abolished the stimulatory role of H2 S on MEF2c/MRF4 heterodimer formation. These findings support an essential role for H2 S in maintaining myogenesis, presenting it as a potential candidate for the prevention of age-related sarcopenia and treatment of muscle injury.
- Subjects :
- 0301 basic medicine
Cell signaling
Chemistry
Myogenesis
Cellular differentiation
Cystathionine gamma-lyase
Skeletal muscle
Biochemistry
Cell biology
03 medical and health sciences
030104 developmental biology
0302 clinical medicine
medicine.anatomical_structure
Genetics
medicine
Myocyte
Molecular Biology
C2C12
030217 neurology & neurosurgery
Myogenin
Biotechnology
Subjects
Details
- ISSN :
- 15306860 and 08926638
- Volume :
- 35
- Database :
- OpenAIRE
- Journal :
- The FASEB Journal
- Accession number :
- edsair.doi...........fac4529931d8ba8138a55bbc4c7b7343