title: Vitamin D upregulates glutamate cysteine ligase and glutathione reductase, and GSH formation, and decreases ROS and MCP-1 and IL-8 secretion in high-glucose exposed U937 monocytes.
abstract: BACKGROUND
  Glutathione is a major endogenous antioxidant and its deficiency is implicated in the etiology and progression of a number of human diseases. Vitamin D is important for the prevention of osteoporosis, cardiovascular disease, diabetes, autoimmune diseases, and some cancers. Using a monocyte cell model, this study examined the hypothesis that vitamin D upregulate glutamate cysteine ligase (GCLC) and glutathione reductase (GR), which catalyzes GSH biosynthesis.
  
  
  METHODS
  U937 monocytes were pretreated with and without 1,25 (OH)₂ vitamin D (10-25 nM) for 24 h and then exposed to control and high glucose (HG, 25 mM) for 4h. Levels of GSH determined using HPLC; GR activity by oxidation of NADPH; GCLC protein, MCP-1 and IL-8 using ELISA kits.
  
  
  RESULTS
  1,25 (OH)₂ vitamin D supplementation significantly upregulated expression of GCLC and GR, levels of GCLC protein and GR activity, and formation of GSH in control and HG-treated monocytes. 1,25 (OH)₂ vitamin D caused significantly (p<0.05) lower secretion of IL-8 and MCP-1, and lower ROS levels in monocytes exposed to control and HG-treated monocytes.
  
  
  CONCLUSIONS
  This study demonstrates a positive link between vitamin D and GSH levels, and that some beneficial effects of vitamin D supplementation may be mediated by an improvement in the cellular GSH levels and a decrease in ROS and pro-inflammatory cytokines.
authors.affiliation: Department of Pediatrics, Louisiana State University Health Sciences Center, Shreveport, LA 71130, United States. sjain@lsuhsc.edu
authors.forename: Sushil K
authors.initials: SK
authors.lastname: Jain
authors.forename: David
authors.initials: D
authors.lastname: Micinski
mesh_terms: D018932:Chemokine CCL2 / Q000378:metabolism*; D005947:Glucose / Q000494:pharmacology*; D005721:Glutamate-Cysteine Ligase / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism*; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism*; D009000:Monocytes / Q000187:drug effects / Q000201:enzymology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D020298:U937 Cells; D015854:Up-Regulation / Q000187:drug effects; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: C111835:CCL2 protein, human; C508606:CXCL8 protein, human; D018932:Chemokine CCL2; D016209:Interleukin-8; D017382:Reactive Oxygen Species; D014807:Vitamin D; C097949:1,25-dihydroxyvitamin D; D005980:Glutathione Reductase; D005721:Glutamate-Cysteine Ligase; D005978:Glutathione; D005947:Glucose
keywords: Diabetes; GCLC; GCLM; GR; GSH; Glutamate cysteine ligase; Glutathione reductase; ROS; Vitamin D; glutamate cysteine ligase catalytic unit; glutamate cysteine ligase modulatory unit; glutathione; glutathione reductase; reactive oxygen species