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.

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.
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DOI:
10.1016/j.bbrc.2013.06.004
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发表时间:
2013-07-19
影响因子:
3.1
通讯作者:
Micinski, David
Micinski, David
中科院分区:
生物学4区
文献类型:
--
作者:
Jain, Sushil K.;Micinski, David

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谷氨酰胺是一种主要的内源性抗氧化剂,其缺乏与许多人类疾病的病因和进展有关。维生素D对预防骨质疏松症、心血管疾病、糖尿病、自身免疫性疾病和某些癌症很重要。使用单核细胞模型,本研究检验了维生素D上调谷氨酸半胱氨酸连接酶(GCLC)和谷胱甘肽还原酶(GR)的假设,这催化GSH的生物合成。U937单核细胞用和不用1,25(OH)维生素D(10 - 25 nM)预处理24小时,然后暴露于对照和高葡萄糖(HG,25 mM)4小时。使用HPLC测定GSH水平;通过NADPH氧化测定GR活性;使用ELISA试剂盒测定GCLC蛋白、MCP-1和IL-8。1,25(OH)2维生素D补充显著上调GCLC和GR的表达,GCLC蛋白和GR活性水平,以及对照和HG处理的单核细胞中GSH的形成。1,25(OH)2维生素D导致暴露于对照和HG处理的单核细胞的单核细胞中显著(p <0.05)较低的IL-8和MCP-1分泌以及较低的ROS水平。这项研究表明维生素D和GSH水平之间存在正相关,补充维生素D的一些有益作用可能是通过改善细胞GSH水平和减少ROS和促炎细胞因子来介导的。
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. U937 monocytes were pretreated with and without 1,25 (OH) vitamin D (10-25 nM) for 24 hr and then exposed to control and high glucose (HG, 25 mM) for 4 hr. Levels of GSH determined using HPLC; GR activity by oxidation of NADPH; GCLC protein, MCP-1 and IL-8 using ELISA kits. 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. 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.
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