期刊
FREE RADICAL BIOLOGY AND MEDICINE
卷 99, 期 -, 页码 1-10出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2016.07.020
关键词
Endothelial cells; 1,25-dihydroxyvitamin D-3; Endoplasmic reticulum stress; Cardiovascular disease
资金
- University of Florida - Jacksonville [70740]
Endoplasmic reticulum (ER) stress and oxidative stress promote endothelial dysfunction and atherosclerosis. Since vitamin D has been shown in several studies to lower the risk of cardiovascular disease, we examined the effects of vitamin Don ER stress and oxidative stress in endothelial cells. ER stress was measured using the placental secreted alkaline phosphatase assay and oxidative stress was measured by hydroethidine fluorescence. Expression of ER stress markers, including glucose-regulated protein 78, cjun N-terminal kinase 1 phosphorylation, and eukaryotic initiation factor 2oc phosphorylation, as well as X-box binding protein-1 splicing were measured in tunicamycin (TM)-treated human umbilical endothelial cells (HUVEC) treated with 1,25-dihydroxyvitamin D-3 (1,25-(OH)(2)D-3) and other vitamin D analogs. When TM and 1,25-(OH)(2)D-3 were added simultaneously, 1,25-(OH)(2)D-3 prevented ER stress. However, the effect was much stronger when cells were pre-treated with 1,25-(OH)(2)D-3 for 24-h. However, ER stress was not inhibited by 25-OH vitamin D3 (25-OHD3) or the vitamin D analog EB1089. Both ZK191784 and the vitamin D metabolite 24,25-dihydroxyvitamin D-3 were as effective as 1,25-(OH)(2)D-3 in preventing ER stress. Similar effects were observed dextrose-induced stress. All of the compounds tested, except for 25-OHD3, inhibited dextrose-induced (27.5 mM) oxidative stress and ER stress. Although TM with and without 1,25-(OH)(2)D-3 had no effect on VDR expression, inhibition of VDR expression via siRNA prevented 1,25-(OH)(2)D-3, ZK191784, EB1089, and 24,25-dihydroxyvitamin D-3 from inhibiting dextrose mediated SO generation. Furthermore, each vitamin D analog, with the exception of 25-OHD3, prevented dextrose-induced toxicity. These results suggest that vitamin D has a protective effect on vascular endothelial cells. (C) 2016 Elsevier Inc. All rights reserved.
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