PMID- 31089421 OWN - NLM STAT- MEDLINE DCOM- 20191220 LR - 20220408 IS - 1942-0994 (Electronic) IS - 1942-0900 (Print) IS - 1942-0994 (Linking) VI - 2019 DP - 2019 TI - Endogenous CSE/Hydrogen Sulfide System Regulates the Effects of Glucocorticoids and Insulin on Muscle Protein Synthesis. PG - 9752698 LID - 10.1155/2019/9752698 [doi] LID - 9752698 AB - 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 (H(2)S) is a physiological mediator of this process. The regulatory effect of H(2)S 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 gamma-lyase (CSE) protein in myoblasts. The precursor of H(2)S, 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 H(2)S donor NaHS increased the H(2)S 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/H(2)S regulated protein synthesis in fast-twitch muscle fibres, and glucocorticoids and insulin regulated protein synthesis in an endogenous CSE/H(2)S system-dependent manner. CONCLUSIONS: The results from the present study suggest that the endogenous CSE/H(2)S system regulates fast-twitch glycolytic muscle degeneration and regeneration. FAU - Wang, Ruxia AU - Wang R AD - Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Shandong Agricultural University, 61 Daizong Street, Taian City, Shandong Province 271018, China. FAU - Li, Kelin AU - Li K AD - Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Shandong Agricultural University, 61 Daizong Street, Taian City, Shandong Province 271018, China. FAU - Wang, Hui AU - Wang H AD - Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Shandong Agricultural University, 61 Daizong Street, Taian City, Shandong Province 271018, China. FAU - Jiao, Hongchao AU - Jiao H AD - Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Shandong Agricultural University, 61 Daizong Street, Taian City, Shandong Province 271018, China. FAU - Wang, Xiaojuan AU - Wang X AD - Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Shandong Agricultural University, 61 Daizong Street, Taian City, Shandong Province 271018, China. FAU - Zhao, Jingpeng AU - Zhao J AD - Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Shandong Agricultural University, 61 Daizong Street, Taian City, Shandong Province 271018, China. FAU - Lin, Hai AU - Lin H AUID- ORCID: 0000-0002-0878-137X AD - Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Shandong Agricultural University, 61 Daizong Street, Taian City, Shandong Province 271018, China. LA - eng PT - Journal Article DEP - 20190407 PL - United States TA - Oxid Med Cell Longev JT - Oxidative medicine and cellular longevity JID - 101479826 RN - 0 (Alkynes) RN - 0 (Glucocorticoids) RN - 0 (Insulin) RN - 0 (Muscle Proteins) RN - 0 (Receptors, Glucocorticoid) RN - 320T6RNW1F (Mifepristone) RN - 64165-64-6 (propargylglycine) RN - 7S5I7G3JQL (Dexamethasone) RN - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - EC 4.4.1.1 (Cystathionine gamma-Lyase) RN - K848JZ4886 (Cysteine) RN - TE7660XO1C (Glycine) RN - YY9FVM7NSN (Hydrogen Sulfide) SB - IM MH - Alkynes/pharmacology MH - Animals MH - Chickens MH - Cystathionine gamma-Lyase/*metabolism MH - Cysteine/pharmacology MH - Dexamethasone/pharmacology MH - Glucocorticoids/*pharmacology MH - Glycine/analogs & derivatives/pharmacology MH - Hydrogen Sulfide/*metabolism MH - Injections, Intraperitoneal MH - Insulin/*pharmacology MH - Mifepristone/pharmacology MH - Muscle Proteins/*biosynthesis MH - Myoblasts/drug effects/metabolism MH - Phosphorylation/drug effects MH - Protein Biosynthesis/*drug effects MH - Receptors, Glucocorticoid/metabolism MH - Ribosomal Protein S6 Kinases, 70-kDa/metabolism MH - Signal Transduction/drug effects MH - TOR Serine-Threonine Kinases/metabolism PMC - PMC6476024 EDAT- 2019/05/16 06:00 MHDA- 2019/12/21 06:00 PMCR- 2019/04/07 CRDT- 2019/05/16 06:00 PHST- 2018/09/04 00:00 [received] PHST- 2018/11/09 00:00 [revised] PHST- 2018/12/18 00:00 [accepted] PHST- 2019/05/16 06:00 [entrez] PHST- 2019/05/16 06:00 [pubmed] PHST- 2019/12/21 06:00 [medline] PHST- 2019/04/07 00:00 [pmc-release] AID - 10.1155/2019/9752698 [doi] PST - epublish SO - Oxid Med Cell Longev. 2019 Apr 7;2019:9752698. doi: 10.1155/2019/9752698. eCollection 2019.