Vitamin D protects human endothelial cells from oxidative stress through the autophagic and survival pathways
F Uberti, D Lattuada, V Morsanuto… - The Journal of …, 2014 - academic.oup.com
F Uberti, D Lattuada, V Morsanuto, U Nava, G Bolis, G Vacca, DF Squarzanti, C Cisari…
The Journal of Clinical Endocrinology & Metabolism, 2014•academic.oup.comContext: 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 …
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 …
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 200μM 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.
Oxford University Press