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

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.

Author information

1
Department of Pediatrics, Louisiana State University Health Sciences Center, Shreveport, LA 71130, United States. sjain@lsuhsc.edu

Abstract

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

PMID:
23770363
PMCID:
PMC4063448
DOI:
10.1016/j.bbrc.2013.06.004
[Indexed for MEDLINE]
Free PMC Article

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