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

Biochem Biophys Res Commun. 2013 Jul 19;437(1):7-11. doi: 10.1016/j.bbrc.2013.06.004. Epub 2013 Jun 11.


Introduction: 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.

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.

Publication types

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

MeSH terms

  • Chemokine CCL2 / metabolism*
  • Glucose / pharmacology*
  • Glutamate-Cysteine Ligase / metabolism*
  • Glutathione / metabolism
  • Glutathione Reductase / metabolism*
  • Humans
  • Interleukin-8 / metabolism*
  • Monocytes / drug effects
  • Monocytes / enzymology*
  • Reactive Oxygen Species / metabolism
  • U937 Cells
  • Up-Regulation / drug effects
  • Vitamin D / analogs & derivatives*
  • Vitamin D / pharmacology


  • CCL2 protein, human
  • CXCL8 protein, human
  • Chemokine CCL2
  • Interleukin-8
  • Reactive Oxygen Species
  • Vitamin D
  • 1,25-dihydroxyvitamin D
  • Glutathione Reductase
  • Glutamate-Cysteine Ligase
  • Glutathione
  • Glucose