Abstract
The aim of this study was to evaluate the influence of resveratrol on HG-induced calcium entry in islet microvascular (MS-1) endothelial cells. MS-1 cells were pretreated with resveratrol or 2-APB (an inhibitor of store-operated calcium entry) and then incubated with high glucose. Cell viability was determined using the cell counting kit-8 method. Reactive oxygen species, endothelial apoptosis, and NO production were detected by DHE probe, TUNEL detection, and nitrate reductase assay kit. Protein levels of SOCE were detected by western blotting. Pretreatment with resveratrol significantly attenuated HG-induced endothelial apoptosis and improved cell viability. However, pretreatment with resveratrol and 2-APB abolished this effect, suggesting that the attenuation of HG-induced apoptosis by resveratrol may be associated with SOCE. Subsequent analyses indicated that HG induced the SOCE-related proteins, including TRPC1, Orai1, and Stim1. These results suggest that resveratrol pretreatment is associated with relieved HG-induced endothelial apoptosis at least partly via inhibition of SOCE-related proteins.
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Acknowledgements
We thank Fang LI for technique assistance in measuring intracellular Ca2+. The study was supported by Chongqing characteristics of specialist construction funds.
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Qiang Xu conceived of the study. Ting Lu carried out cell culture and Western blotting analysis, participated in TUNEL staining, and measurement of intracellular Ca2+. Dayan Zhou performed the statistical analysis. Pan Gao drafted the manuscript. Liangyi Si participated in the design of the study. All authors contributed to and have approved the final manuscript.
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11010_2017_3194_MOESM1_ESM.tif
Supplemental Fig. 1 Scheme image of the signaling mechanisms underlying inhibitory effect of resveratrol for high glucose-induced endothelial cell apoptosis via mediation of store-operated calcium entry. Calcium ion receptor (Stim1), which locates in the endoplasmic reticulum, was found to form Ca2+ channel with Orai1 when the TG was induced to release Ca2+ from the endoplasmic reticulum. High-glucose stimulates apoptosis of endothelial cells via induction of calcium influx through the activation of the SOC channel. Resveratrol functions via inhibiting the activation of the SOC channel to reduce calcium influx, and also via reducing the high glucose-induced reactive oxygen species generation, thereby reducing endothelial cell apoptosis. Supplementary material 1 (TIFF 12837 kb)
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Lu, T., Zhou, D., Gao, P. et al. Resveratrol attenuates high glucose-induced endothelial cell apoptosis via mediation of store-operated calcium entry. Mol Cell Biochem 442, 73–80 (2018). https://doi.org/10.1007/s11010-017-3194-7
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DOI: https://doi.org/10.1007/s11010-017-3194-7