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

• Glutathione is a major endogenous antioxidant.
• Vitamin D is important for the prevention of metabolic diseases.
• This study demonstrates that vitamin D upregulate GSH biosynthesis.
• Vitamin D upregulate glutamate cysteine ligase and glutathione reductase.
• Beneficial effects of vitamin D may be mediated by increase in the cellular GSH.

IntroductionGlutathione 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.MethodsU937 monocytes were pretreated with and without 1,25 (OH) vitamin D (10–25 nM) for 24 h and then exposed to control and high glucose (HG, 25 mM) for 4 h. Levels of GSH determined using HPLC; GR activity by oxidation of NADPH; GCLC protein, MCP-1 and IL-8 using ELISA kits.Results1,25 (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.ConclusionsThis 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.