|作者：||Marampon F, Gravina G L, Festuccia C, Popov V M, Colapietro E A, Sanità P, Musio D, De Felice F, Lenzi A, Jannini E A, Di Cesare E, Tombolini V|
1Division of Radiotherapy and Radiobiology, Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy.
2Division of Radiotherapy and Radiobiology, Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy. email@example.com.
3Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA, USA.
4Department of Radiotherapy, Policlinico Umberto I "Sapienza" University of Rome, Rome, Italy.
5Department of Radiotherapy, Policlinico Umberto I "Sapienza" University of R
|刊名：||Journal of endocrinological investigation, 2016, Vol.39 (4), pp.411-22|
|关键词：||Endothelium; Oxidative stress; Radiotherapy; SirT1; Vitamin D;|
|原始语种摘要：||PURPOSE(#br)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).(#br)METHODS(#br)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.(#br)RESULTS(#br)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.(#br)CONCLUSION(#br)Vit.D protects HUVEC from IR induced/oxidative stress by positively regulating the MAPKs/SirT1 axis.|