F Uberti1, D Lattuada, V Morsanuto, U Nava, G Bolis, G Vacca, D F Squarzanti, C Cisari, C Molinari. 1. Department of Obstetrics and Gynecology (F.U., D.L., V.M., U.N.), Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Ca' Granda, Ospedale Maggiore Policlinico, 20122 Milan, Italy; Dipartimento di Scienze Cliniche e di Comunità (G.B.), Università degli Studi di Milano, 20122, Milan, Italy Dipartimento di Medicina Traslazionale (V.M., G.V., D.F.S., C.M.), Università degli Studi del Piemonte Orientale A. Avogadro, 28100 Novara, Italy; and Dipartimento di Scienze della Salute (C.C.), Università degli Studi del Piemonte Orientale A. Avogadro, 28100 Novara, Italy.
Abstract
CONTEXT: Recently, vitamin D (VitD) has been recognized as increasingly importance in many cellular functions of several tissues and organs other than bone. In particular, VitD showed important beneficial effects in the cardiovascular system. Although the relationship among VitD, endothelium, and cardiovascular disease is well established, little is known about the antioxidant effect of VitD. OBJECTIVE: Our objective was to study the intracellular pathways activated by VitD in cultured human umbilical vein endothelial cells undergoing oxidative stress. DESIGN: Nitric oxide production, cell viability, reactive oxygen species, the mitochondrial permeability transition pore, membrane potential, and caspase-3 activity were measured during oxidative stress induced by administration of 200 μM hydrogen peroxide for 20 minutes. Experiments were repeated in the presence of specific vitamin D receptor ligand ZK191784. RESULTS: Pretreatment with VitD alone or in combination with ZK191784 is able to reduce the apoptosis-related gene expression, involving both intrinsic and extrinsic pathways. At the same time, it has been shown the activation of pro-autophagic beclin 1 and the phosphorylation of ERK1/2 and Akt, indicating a modulation between apoptosis and autophagy. Moreover, VitD alone or in combination with ZK191784 is able to prevent the loss of mitochondrial potential and the consequent cytochrome C release and caspase activation. CONCLUSIONS: The present study shows that VitD may prevent endothelial cell death through modulation of the interplay between apoptosis and autophagy. This effect is obtained by inhibiting superoxide anion generation, maintaining mitochondria function and cell viability, activating survival kinases, and inducing NO production.
CONTEXT: Recently, vitamin D (VitD) has been recognized as increasingly importance in many cellular functions of several tissues and organs other than bone. In particular, VitD showed important beneficial effects in the cardiovascular system. Although the relationship among VitD, endothelium, and cardiovascular disease is well established, little is known about the antioxidant effect of VitD. OBJECTIVE: Our objective was to study the intracellular pathways activated by VitD in cultured human umbilical vein endothelial cells undergoing oxidative stress. DESIGN:Nitric oxide production, cell viability, reactive oxygen species, the mitochondrial permeability transition pore, membrane potential, and caspase-3 activity were measured during oxidative stress induced by administration of 200 μM hydrogen peroxide for 20 minutes. Experiments were repeated in the presence of specific vitamin D receptor ligand ZK191784. RESULTS: Pretreatment with VitD alone or in combination with ZK191784 is able to reduce the apoptosis-related gene expression, involving both intrinsic and extrinsic pathways. At the same time, it has been shown the activation of pro-autophagic beclin 1 and the phosphorylation of ERK1/2 and Akt, indicating a modulation between apoptosis and autophagy. Moreover, VitD alone or in combination with ZK191784 is able to prevent the loss of mitochondrial potential and the consequent cytochrome C release and caspase activation. CONCLUSIONS: The present study shows that VitD may prevent endothelial cell death through modulation of the interplay between apoptosis and autophagy. This effect is obtained by inhibiting superoxide anion generation, maintaining mitochondria function and cell viability, activating survival kinases, and inducing NO production.
Authors: Anna Piotrowska; Justyna Wierzbicka; Tomasz Ślebioda; Michał Woźniak; Robert C Tuckey; Andrzej T Slominski; Michał A Żmijewski Journal: Steroids Date: 2016-04-13 Impact factor: 2.668
Authors: Youssef M K Farag; Eliseo Guallar; Di Zhao; Rita R Kalyani; Michael J Blaha; David I Feldman; Seth S Martin; Pamela L Lutsey; Kevin L Billups; Erin D Michos Journal: Atherosclerosis Date: 2016-07-29 Impact factor: 5.162
Authors: Marc Blondon; Mary Cushman; Nancy Jenny; Erin D Michos; Nicholas L Smith; Bryan Kestenbaum; Ian H de Boer Journal: J Clin Endocrinol Metab Date: 2016-03-29 Impact factor: 5.958