Vitamin D prevents high glucose-induced human umbilical vein endothe-lial cell apoptosis by inhibition of prolyl isomerase 1-mediated mitochon-drial oxidative stress
10.3969/j.issn.1000-4718.2018.01.003
- VernacularTitle:维生素D通过抑制Pin1介导线粒体氧化应激拮抗高糖诱导的人脐静脉内皮细胞凋亡
- Author:
Li-Ming LIN
1
;
Mei-Jin ZHANG
;
Chang-Sheng XU
;
Jin-Xiu LIN
Author Information
1. 莆田学院附属医院心内科
- Keywords:
Vitamin D;
Prolyl isomerase 1;
High glucose;
Human umbilical vein endothelial cells;
Mito-chondrial oxidative stress
- From:
Chinese Journal of Pathophysiology
2018;34(1):15-21
- CountryChina
- Language:Chinese
-
Abstract:
AIM:To observe the effects of vitamin D on the apoptosis ,prolyl isomerase 1(Pin1)protein ex-pression and activity ,mitochondrial translocation of p 66Shc,and reactive oxygen species(ROS)production in high glu-cose-cultured human umbilical vein endothelial cells(HUVECs),and to explore the role of vitamin D receptor(VDR)in these processes.METHODS:HUVECs were treated with high glucose(33 mmol/L)in the presence or absence of vita-min D or Pin1 inhibitor juglone.The cell apoptosis was measured by flow cytometry and TUNEL staining.Intracellular ROS levels were examined by flow cytometry and fluorescence microscopy.The protein levels of Pin1,p66Shc,p-p66Shc,mito-chondria to cytoplasm ratio of p66Shc,and caspase-3 in HUVECs were measured by Western blot.Pin1 activity in HU-VECs lysate was assessed by a commercial kit.Knockdown of VDR by siRNA was conducted to evaluate the role of VDR in the regulatory effects of vitamin D on Pin 1 protein expression and activity in HUVECs under high-glucose condition.RE-SULTS:Vitamin D suppressed the apoptosis and intracellular ROS generation of HUVECs induced by high glucose(P<0.05).Vitamin D inhibited high glucose-induced upregulation of Pin1 protein expression and activity(P<0.05).Vita-min D inhibited the phosphorylation and mitochondrial translocation of p 66Shc and caspase-3 protein expression induced by high glucose(P<0.05).Knockdown of VDR by siRNA abolished the inhibitory effects of vitamin D on high glucose-in-duced upregulation of Pin 1 protein expression and activity.CONCLUSION:Vitamin D alleviates high glucose-induced endothelial cell apoptosis by inhibition of Pin 1 protein expression and activity ,and attenuation of p66Shc-mediated mito-chondrial oxidative stress ,which are dependent on VDR activation.
