1, 25(OH)2D3 inhibits oxidative stress and monocyte adhesion by mediating the upregulation of GCLC and GSH in endothelial cells treated with acetoacetate (ketosis). Issue 159 (May 2016)

• Record Type: Journal Article
• Authors: Kanikarla-Marie, Preeti; Jain, Sushil K.
• Is Part Of: Journal of steroid biochemistry and molecular biology. Issue 159(2016)
• Page Start: 94
• Page End: 101
• Publication Date: 2016-05
• Subjects: CVD cardiovascular disease -- T1D type 1 diabetes -- VD vitamin D -- AA acetoacetate -- ROS reactive oxygen species -- ICAM-1 intercellular adhesion molecule-1 -- MCP-1 monocyte chemotactic protein-1 -- GSH glutathione -- GCLC glutamate cysteine ligase catalytic subunit -- TNFT-α Tumor necrosis factor alpha -- VCAM-1 vascular cell adhesion molecule-1 -- IL-8 interleukin-8; Vitamin D -- 1, 25(OH)2D3 -- Oxidative stress -- Endothelium -- Ketones -- Type 1 diabetes; Steroid hormones -- Periodicals; Biochemistry -- Periodicals; Hormones -- Periodicals; Molecular Biology -- Periodicals; Hormones stéroïdes -- Périodiques; Steroid hormones; Periodicals; 572.579
• DOI: 10.1016/j.jsbmb.2016.03.002
• Languages: English
• ISSNs: 0960-0760

Abstract

Highlights: 1, 25(OH)2 vitamin D inhibits ketone induced oxidative stress and monocyte adhesion in HUVEC. Beneficial effects of 1, 25(OH)2 vitamin D are impaired in cells that are deficient in glutathione. 1, 25(OH)2 vitamin D upregulates glutathione in a vitamin D receptor-dependent manner. Abstract: Background: There is a significantly higher incidence of cardiovascular disease (CVD) among type 1 diabetic (T1D) patients than among non-diabetic subjects. T1D is associated with hyperketonemia, a condition with elevated blood levels of ketones, in addition to hyperglycemia. The biochemical mechanism by which vitamin D (VD) may reduce the risk of CVD is not known. This study examines whether VD can be beneficial in reducing hyperketonemia (acetoacetate, AA) induced oxidative stress in endothelial cells. Methods: HUVEC were pretreated with 1, 25(OH)2 D3, and later exposed to the ketone body acetoacetate. Results: The increases in ROS production, ICAM-1 expression, MCP-1 secretion, and monocyte adhesion in HUVEC treated with AA were significantly reduced following treatment with 1, 25(OH)2 D3 . Interestingly, an increase in glutathione (GSH) levels was also observed with 1, 25(OH)2 D3 in ketone treated cells. The effects of 1, 25(OH)2 D3 on GSH, ROS, and monocyte-endothelial adhesion were prevented in GCLC knockdown HUVEC. This suggests that 1, 25(OH)2 D3 inhibits ROS, MCP-1, ICAM-1, and adherence of monocytes mediated by the upregulation of GCLC and GSH. Conclusion: This study provides evidence for the biochemical mechanism through which VD supplementation may reduce the excess monocyte adhesion to endothelium and inflammation associated with T1D.