Vitamin D protects human endothelial cells from H₂O₂ oxidant injury through the Mek/Erk-Sirt1 axis activation

"Endothelium homeostasis alterations govern. the pathogenesis of cardiovascular diseases. Several. studies show that vitamins anti-oxidant proprieties rescue. the endothelial functions adversely affected by. oxidative stress in several diseases. We investigated the. vitamin D anti-oxidant potential in human endothelial cells. exposed to H2O2 oxidative stress. Vitamin D protected. endothelial cells against H2O2 oxidative stress counteracting. the superoxide anion generation, the apoptosis and. blocking the extrinsic caspase cascade by positively controlling. phospho-active ERKs level. MEKs\/ERKs inhibitor. U0126 reverted the vitamin D anti-oxidant effects. Characterizing. the vitamin D downstream effector, we found. that vitamin D up-regulated SirT-1 and reverted the SirT-1. down-regulation induced by H2O2. ERKs activation by. vitamin D strictly correlated with SirT-1 protein accumulation. since both MEKs\/ERKs inhibition and ERK1\/2 silencing. decreased SIRT-1. SirT-1 inhibition by Sirtinol. reverted the vitamin D anti-oxidant effects. Thus, vitamin. D significantly reduced the endothelial malfunction and. damage caused by oxidative stress, through the activation. of MEKs\/ERKs\/SirT-1 axis."