title: Hydrogen sulfide upregulates glutamate-cysteine ligase catalytic subunit, glutamate-cysteine ligase modifier subunit, and glutathione and inhibits interleukin-1β secretion in monocytes exposed to high glucose levels.
abstract: Glutathione (GSH) deficiency and interleukin-1β (IL-1β) upregulation are linked to the progression of vascular inflammation and atherosclerosis. The consumption of sulfide-rich vegetables is known to lower the risk of atherosclerosis. This study examined the hypothesis that hydrogen sulfide (H2S) upregulates the glutamate-cysteine ligase catalytic subunit (GCLC) and GSH and inhibits IL-1β in a monocyte cell model. U937 monocytes were supplemented with H2S (0-12.5 μM) for 2 hr and then exposed to a control or high glucose (HG, 25 mM) for 22 hr. Levels of GCLC and glutamate-cysteine ligase modifier subunit (GCLM) expression were determined by western blotting and GSH using high-performance liquid chromatography (HPLC), and IL-1β using enzyme-linked immunoassay (ELISA). H2S significantly (P<0.05) upregulated expression of GCLC and GCLM, and formation of GSH, and inhibited IL-1β secretion in controls and HG-treated monocytes. This is the first demonstration of H2S upregulation of GCLC and GSH and inhibition of IL-1β levels, which may be what mediates the beneficial effects of H2S-rich compounds in mitigating the pathogenesis of metabolic syndrome and atherosclerosis.
authors.affiliation: Department of Pediatrics, Louisiana State University Health Sciences Center , Shreveport, Louisiana.
authors.forename: Sushil K
authors.initials: SK
authors.lastname: Jain
authors.forename: Laura
authors.initials: L
authors.lastname: Huning
authors.forename: David
authors.initials: D
authors.lastname: Micinski
mesh_terms: D050197:Atherosclerosis; D020134:Catalytic Domain; D002470:Cell Survival; D004797:Enzyme-Linked Immunosorbent Assay; D005947:Glucose / Q000378:metabolism*; D005721:Glutamate-Cysteine Ligase / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D006862:Hydrogen Sulfide / Q000737:chemistry*; D007249:Inflammation; D053583:Interleukin-1beta / Q000097:blood*; D009000:Monocytes / Q000378:metabolism*; D018384:Oxidative Stress; D020298:U937 Cells; D015854:Up-Regulation
chemical_list: D053583:Interleukin-1beta; C546365:GCLM protein, human; D005721:Glutamate-Cysteine Ligase; D005978:Glutathione; D005947:Glucose; D006862:Hydrogen Sulfide