title: S-Propargyl-cysteine (SPRC) attenuated lipopolysaccharide-induced inflammatory response in H9c2 cells involved in a hydrogen sulfide-dependent mechanism.
abstract: The present study attempts to investigate the effects of S-propargyl-cysteine (SPRC), a sulfur-containing amino acid, on lipopolysaccharide (LPS)-induced inflammatory response in H9c2 cardiac myocytes. We found that SPRC prevented nuclear factor-κB (NF-κB) activation assessed by NF-κB p65 phosphorylation and IκBα degradation, suppressed LPS-induced extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation and intracellular reactive oxygen species (ROS) production. Furthermore, incubation of H9c2 cells with SPRC induced phosphorylation of Akt in a time- and concentration-dependent manner. In addition, SPRC attenuated LPS-induced mRNA and protein expression of tumor necrosis factor-α (TNF-α), and mRNA expression of intercellular adhesion molecule-1 (ICAM-1) and inducible nitric oxide synthase (iNOS). The effects of SPRC were abolished by cystathionine γ-lyase [CSE-an enzyme that synthesizes hydrogen sulfide (H(2)S)] inhibitor, DL: -propargylglycine (PAG), SPRC-induced Akt phosphorylation and TNF-α release was also abolished by the phosphoinositide 3-kinase (PI3K) inhibitor LY294002. Furthermore, SPRC also increased LPS-induced down-regulation expression of CSE and H(2)S level in H9c2 cells. PAG abolished SPRC-induced up-regulation of H(2)S level. Therefore, we concluded that SPRC produced an anti-inflammatory effect in LPS-stimulated H9c2 cells partly through the CSE/H(2)S pathway by impairing IκBα/NF-κB signaling and by activating PI3K/Akt signaling pathway.
authors.affiliation: Department of Pharmacology, School of Pharmacy, Institute of Biomedical Sciences, Fudan University, Shanghai, China.
authors.forename: Li-Long
authors.initials: LL
authors.lastname: Pan
authors.forename: Xin-Hua
authors.initials: XH
authors.lastname: Liu
authors.forename: Qi-Hai
authors.initials: QH
authors.lastname: Gong
authors.forename: Yi-Zhun
authors.initials: YZ
authors.lastname: Zhu
mesh_terms: D000818:Animals; D002460:Cell Line; D003545:Cysteine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D006862:Hydrogen Sulfide / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology / Q000517:prevention & control*; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051381:Rats
chemical_list: D008070:Lipopolysaccharides; C556437:S-propargylcysteine; D003545:Cysteine; D006862:Hydrogen Sulfide