Abstract
Purpose
Radiotherapy toxicity is related to oxidative stress-mediated endothelial dysfunction. Here, we investigated on radioprotective properties of Vitamin D (Vit.D) on human endothelial cells (HUVEC).
Methods
HUVEC, pre-treated with Vit.D, were exposed to ionizing radiation (IR): ROS production, cellular viability, apoptosis, senescence and western blot for protein detection were performed. The role of MAPKs pathway was investigated by using U0126 (10 μM) MEKs/ERKs-, SB203580 (2.5 μM) p38-inhibitor or by over/expressing MKK6 p38-upstream activator.
Results
Vit.D reduced IR-induced ROS production protecting proliferating and quiescent HUVEC from cellular apoptosis or senescence, respectively, by regulating MAPKs pathways. In proliferating HUVEC, Vit.D prevented IR-induced apoptosis by activating ERKs while in quiescent HUVEC counteracted IR-induced senescence by inhibiting the p38-IR-induced activation. MEKs&ERKs inhibition in proliferating or MKK6/mediated p38 activation in quiescent HUVEC, respectively, reverted anti-apoptotic or anti-senescent Vit.D properties. SirT1 protein expression levels were up-regulated by Vit.D. ERKs inhibition blocked Vit.D-induced SirT1 protein up-regulation in proliferating cells. In quiescent HUVEC cells, p38 inhibition counteracted the IR-induced SirT1 protein down-regulation, while MKK6 transfection abrogated the Vit.D positive effects on SirT1 protein levels after irradiation. SirT1 inhibition by sirtinol blocked the Vit.D radioprotective effects.
Conclusion
Vit.D protects HUVEC from IR induced/oxidative stress by positively regulating the MAPKs/SirT1 axis.
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Change history
05 June 2020
Unfortunately, the 5th author name has been publisehd incorrectly in the original publication. The complete correct name is given below.
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Professor Jannini has been or is speaker and consultant of Janseen; Bayer, Lilly; JSK; IBSA; Pfizer and Menarini. All other authors declare no conflict of interest.
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F. Marampon and G. L. Gravina contributed equally.
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Marampon, F., Gravina, G.L., Festuccia, C. et al. Vitamin D protects endothelial cells from irradiation-induced senescence and apoptosis by modulating MAPK/SirT1 axis. J Endocrinol Invest 39, 411–422 (2016). https://doi.org/10.1007/s40618-015-0381-9
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DOI: https://doi.org/10.1007/s40618-015-0381-9