Resveratrol attenuates high glucose-induced endothelial cell apoptosis via mediation of store-operated calcium entry
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.
KeywordsResveratrol Store-operated calcium entry (SOCE) Endothelial cells Apoptosis High glucose
We thank Fang LI for technique assistance in measuring intracellular Ca2+. The study was supported by Chongqing characteristics of specialist construction funds.
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.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no competing interests.
- 1.Mylroie H, Dumont O, Bauer A, Thornton CC, Mackey J, Calay D, Hamdulay SS, Choo JR, Boyle JJ, Samarel AM (2015) PKCε-CREB-Nrf2 signalling induces HO-1 in the vascular endothelium and enhances resistance to inflammation and apoptosis. Cardiovasc Res 106:509–519CrossRefPubMedPubMedCentralGoogle Scholar
- 8.Quagliaro L, Piconi L, Assaloni R, Martinelli L, Motz E, Ceriello A (2003) Intermittent high glucose enhances apoptosis related to oxidative stress in human umbilical vein endothelial cells the role of protein kinase C and NAD(P)H-oxidase activation. Diabetes 52:2795–2804CrossRefPubMedGoogle Scholar
- 12.Zhang M, Song J-N, Wu Y, Zhao Y-L, Pang H-G, Fu Z-F, Zhang B-F, Ma X-D (2014) Suppression of STIM1 in the early stage after global ischemia attenuates the injury of delayed neuronal death by inhibiting store-operated calcium entry-induced apoptosis in rats. NeuroReport 25:507–513PubMedGoogle Scholar
- 20.Selvaraj S, Sun Y, Sukumaran P, Singh BB (2015) Resveratrol activates autophagic cell death in prostate cancer cells via downregulation of STIM1 and the mTOR pathway. Mol CarcinogGoogle Scholar
- 25.Sun Y, Cui X, Wang J, Wu S, Bai Y, Wang Y, Wang B, Fang J (2015) Stromal interaction molecule 1 (STIM1) silencing inhibits tumor growth and promotes cell cycle arrest and apoptosis in hypopharyngeal carcinoma. Med Oncol 32:608Google Scholar
- 26.Raphaël M, Lehen’Kyi V, Vandenberghe M, Beck B, Khalimonchyk S, Vanden AF, Farsetti L, Germain E, Bokhobza A, Mihalache A (2014) TRPV6 calcium channel translocates to the plasma membrane via Orai1-mediated mechanism and controls cancer cell survival. Proc Natl Acad Sci USA 111:3870–3879CrossRefGoogle Scholar