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Hydrogen sulfide regulates circadian-clock genes in C2C12 myotubes and the muscle of high-fat-diet-fed mice.
Arch Biochem Biophys. 2019 09 15; 672:108054.AB

Abstract

Hydrogen sulfide (H2S) is an endogenous novel gasotransmitter which is implicated in the pathophysiology of the metabolic syndrome. Core clock genes (CCG) and its controlled genes disruption is implicated in the progression of metabolic syndrome. We examined whether H2S has any effect on CCG in the skeletal muscle of mice fed a high-fat diet (HFD) and in myotubes. In the muscle of HFD-mice, the expression of H2S biosynthesis enzyme genes (CSE, CBS, and 3-Mpst) along with antioxidant genes (GCLC, GCLM, GSS, and GSR) involved in GSH biosynthesis and recycling were reduced significantly, but the oxidative stress (OS) increased. Expression of the CCG (Bmal1, Clock, RORα, Cry2, Per2) and clock-controlled genes (PPARγ, PGC-1α, RXRα) was downregulated, whereas the levels of PPARα mRNA were upregulated. Similar to that in the muscle of HFD-mice, in vitro myotubes exposed to high glucose or palmitate to mimic metabolic syndrome, showed an increased OS and decreased in CSE mRNA, H2S production and CCG mRNA levels were also downregulated. TNF and MCP-1 treatment on the myotubes was similar to that observed in HFD-muscle, with that the Rev-erbα mRNA was upregulated. Inhibition (siRNA/pharmacological inhibitors) of both CSE and GCLC (the rate-limiting enzyme in GSH biosynthesis) decreased H2S, and increased OS; Bmal1 and Clock mRNA levels were downregulated, while Rev-erbα increased significantly in these conditions. CSE KD myotubes were post-treated with an H2S donor partially restored the mRNA levels of core clock genes. These findings report that the deficiencies of H2S/GSH impair expression of CCG and treatment with H2S donor or GSH precursor exert a positive effect over CCG. Thus, suggest that H2S as a new endogenous factor for regulating circadian clock, and its donors could provide a novel chrono-pharmacological therapy to manage metabolic disorders.

Authors+Show Affiliations

Department of Pediatrics and Center for Cardiovascular Diseases and Sciences, Louisiana State University Health Sciences Center-Shreveport, 1501 Kings Highway, Shreveport, LA, 71130, USA.Department of Pediatrics and Center for Cardiovascular Diseases and Sciences, Louisiana State University Health Sciences Center-Shreveport, 1501 Kings Highway, Shreveport, LA, 71130, USA. Electronic address: sjain@lsuhsc.edu.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

31351068

Citation

Parsanathan, Rajesh, and Sushil K. Jain. "Hydrogen Sulfide Regulates Circadian-clock Genes in C2C12 Myotubes and the Muscle of High-fat-diet-fed Mice." Archives of Biochemistry and Biophysics, vol. 672, 2019, p. 108054.
Parsanathan R, Jain SK. Hydrogen sulfide regulates circadian-clock genes in C2C12 myotubes and the muscle of high-fat-diet-fed mice. Arch Biochem Biophys. 2019;672:108054.
Parsanathan, R., & Jain, S. K. (2019). Hydrogen sulfide regulates circadian-clock genes in C2C12 myotubes and the muscle of high-fat-diet-fed mice. Archives of Biochemistry and Biophysics, 672, 108054. https://doi.org/10.1016/j.abb.2019.07.019
Parsanathan R, Jain SK. Hydrogen Sulfide Regulates Circadian-clock Genes in C2C12 Myotubes and the Muscle of High-fat-diet-fed Mice. Arch Biochem Biophys. 2019 09 15;672:108054. PubMed PMID: 31351068.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hydrogen sulfide regulates circadian-clock genes in C2C12 myotubes and the muscle of high-fat-diet-fed mice. AU - Parsanathan,Rajesh, AU - Jain,Sushil K, Y1 - 2019/07/24/ PY - 2019/06/07/received PY - 2019/07/18/revised PY - 2019/07/24/accepted PY - 2019/7/28/pubmed PY - 2020/3/24/medline PY - 2019/7/28/entrez KW - Core clock genes (CCG) KW - Glutathione (GSH) KW - Hydrogen sulfide (H(2)S) KW - Oxidative stress (OS) SP - 108054 EP - 108054 JF - Archives of biochemistry and biophysics JO - Arch. Biochem. Biophys. VL - 672 N2 - Hydrogen sulfide (H2S) is an endogenous novel gasotransmitter which is implicated in the pathophysiology of the metabolic syndrome. Core clock genes (CCG) and its controlled genes disruption is implicated in the progression of metabolic syndrome. We examined whether H2S has any effect on CCG in the skeletal muscle of mice fed a high-fat diet (HFD) and in myotubes. In the muscle of HFD-mice, the expression of H2S biosynthesis enzyme genes (CSE, CBS, and 3-Mpst) along with antioxidant genes (GCLC, GCLM, GSS, and GSR) involved in GSH biosynthesis and recycling were reduced significantly, but the oxidative stress (OS) increased. Expression of the CCG (Bmal1, Clock, RORα, Cry2, Per2) and clock-controlled genes (PPARγ, PGC-1α, RXRα) was downregulated, whereas the levels of PPARα mRNA were upregulated. Similar to that in the muscle of HFD-mice, in vitro myotubes exposed to high glucose or palmitate to mimic metabolic syndrome, showed an increased OS and decreased in CSE mRNA, H2S production and CCG mRNA levels were also downregulated. TNF and MCP-1 treatment on the myotubes was similar to that observed in HFD-muscle, with that the Rev-erbα mRNA was upregulated. Inhibition (siRNA/pharmacological inhibitors) of both CSE and GCLC (the rate-limiting enzyme in GSH biosynthesis) decreased H2S, and increased OS; Bmal1 and Clock mRNA levels were downregulated, while Rev-erbα increased significantly in these conditions. CSE KD myotubes were post-treated with an H2S donor partially restored the mRNA levels of core clock genes. These findings report that the deficiencies of H2S/GSH impair expression of CCG and treatment with H2S donor or GSH precursor exert a positive effect over CCG. Thus, suggest that H2S as a new endogenous factor for regulating circadian clock, and its donors could provide a novel chrono-pharmacological therapy to manage metabolic disorders. SN - 1096-0384 UR - https://www.unboundmedicine.com/medline/citation/31351068/Hydrogen_sulfide_regulates_circadian_clock_genes_in_C2C12_myotubes_and_the_muscle_of_high_fat_diet_fed_mice_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0003-9861(19)30441-2 DB - PRIME DP - Unbound Medicine ER -