1,25(OH)                         2                         D                         3                          inhibits oxidative stress and monocyte adhesion by mediating the upregulation of GCLC and GSH in endothelial cells treated with acetoacetate (ketosis)

Preeti Kanikarla-Marie; Sushil K. Jain

doi:10.1016/j.jsbmb.2016.03.002

1,25(OH) ₂ D ₃ inhibits oxidative stress and monocyte adhesion by mediating the upregulation of GCLC and GSH in endothelial cells treated with acetoacetate (ketosis)

Preeti Kanikarla-Marie, Sushil K. Jain

GI Medical Oncology

Research output: Contribution to journal › Article › peer-review

48 Scopus citations

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 D ₃ , 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 D ₃ . Interestingly, an increase in glutathione (GSH) levels was also observed with 1,25(OH) ₂ D ₃ in ketone treated cells. The effects of 1,25(OH) ₂ D ₃ on GSH, ROS, and monocyte-endothelial adhesion were prevented in GCLC knockdown HUVEC. This suggests that 1,25(OH) ₂ D ₃ 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.

Original language	English (US)
Pages (from-to)	94-101
Number of pages	8
Journal	Journal of Steroid Biochemistry and Molecular Biology
Volume	159
DOIs	https://doi.org/10.1016/j.jsbmb.2016.03.002
State	Published - May 2016

Keywords

1,25(OH)2D3
Endothelium
Ketones
Oxidative stress
Type 1 diabetes
Vitamin D

ASJC Scopus subject areas

Endocrinology, Diabetes and Metabolism
Biochemistry
Molecular Medicine
Molecular Biology
Endocrinology
Clinical Biochemistry
Cell Biology

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10.1016/j.jsbmb.2016.03.002

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Kanikarla-Marie, P., & Jain, S. K. (2016). 1,25(OH) ₂ D ₃ inhibits oxidative stress and monocyte adhesion by mediating the upregulation of GCLC and GSH in endothelial cells treated with acetoacetate (ketosis) Journal of Steroid Biochemistry and Molecular Biology, 159, 94-101. https://doi.org/10.1016/j.jsbmb.2016.03.002

1,25(OH) ₂ D ₃ inhibits oxidative stress and monocyte adhesion by mediating the upregulation of GCLC and GSH in endothelial cells treated with acetoacetate (ketosis) . / Kanikarla-Marie, Preeti; Jain, Sushil K.
In: Journal of Steroid Biochemistry and Molecular Biology, Vol. 159, 05.2016, p. 94-101.

Research output: Contribution to journal › Article › peer-review

Kanikarla-Marie, P & Jain, SK 2016, ' 1,25(OH) ₂ D ₃ inhibits oxidative stress and monocyte adhesion by mediating the upregulation of GCLC and GSH in endothelial cells treated with acetoacetate (ketosis) ', Journal of Steroid Biochemistry and Molecular Biology, vol. 159, pp. 94-101. https://doi.org/10.1016/j.jsbmb.2016.03.002

Kanikarla-Marie P, Jain SK. 1,25(OH) ₂ D ₃ inhibits oxidative stress and monocyte adhesion by mediating the upregulation of GCLC and GSH in endothelial cells treated with acetoacetate (ketosis) Journal of Steroid Biochemistry and Molecular Biology. 2016 May;159:94-101. doi: 10.1016/j.jsbmb.2016.03.002

Kanikarla-Marie, Preeti ; Jain, Sushil K. / 1,25(OH) ₂ D ₃ inhibits oxidative stress and monocyte adhesion by mediating the upregulation of GCLC and GSH in endothelial cells treated with acetoacetate (ketosis) In: Journal of Steroid Biochemistry and Molecular Biology. 2016 ; Vol. 159. pp. 94-101.

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title = " 1,25(OH) 2 D 3 inhibits oxidative stress and monocyte adhesion by mediating the upregulation of GCLC and GSH in endothelial cells treated with acetoacetate (ketosis) ",

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 D 3 , 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 D 3 . Interestingly, an increase in glutathione (GSH) levels was also observed with 1,25(OH) 2 D 3 in ketone treated cells. The effects of 1,25(OH) 2 D 3 on GSH, ROS, and monocyte-endothelial adhesion were prevented in GCLC knockdown HUVEC. This suggests that 1,25(OH) 2 D 3 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.",

keywords = "1,25(OH)2D3, Endothelium, Ketones, Oxidative stress, Type 1 diabetes, Vitamin D",

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T1 - 1,25(OH) 2 D 3 inhibits oxidative stress and monocyte adhesion by mediating the upregulation of GCLC and GSH in endothelial cells treated with acetoacetate (ketosis)

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AU - Jain, Sushil K.

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N2 - 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 D 3 , 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 D 3 . Interestingly, an increase in glutathione (GSH) levels was also observed with 1,25(OH) 2 D 3 in ketone treated cells. The effects of 1,25(OH) 2 D 3 on GSH, ROS, and monocyte-endothelial adhesion were prevented in GCLC knockdown HUVEC. This suggests that 1,25(OH) 2 D 3 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.

AB - 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 D 3 , 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 D 3 . Interestingly, an increase in glutathione (GSH) levels was also observed with 1,25(OH) 2 D 3 in ketone treated cells. The effects of 1,25(OH) 2 D 3 on GSH, ROS, and monocyte-endothelial adhesion were prevented in GCLC knockdown HUVEC. This suggests that 1,25(OH) 2 D 3 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.

KW - 1,25(OH)2D3

KW - Endothelium

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KW - Type 1 diabetes

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