Propofol protects against high glucose-induced endothelial adhesion molecules expression in human umbilical vein endothelial cells

Minmin Zhu,Jiawei Chen,Hui Jiang,Changhong Miao

doi:10.1186/1475-2840-12-13

Abstract

BackgroundHyperglycemia could induce oxidative stress, activate transcription factor nuclear factor kappa B (NF-κB), up-regulate expression of endothelial adhesion molecules, and lead to endothelial injury. Studies have indicated that propofol could attenuate oxidative stress and suppress NF-κB activation in some situations. In the present study, we examined whether and how propofol improved high glucose-induced up-regulation of endothelial adhesion molecules in human umbilical vein endothelial cells (HUVECs).MethodsProtein expression of endothelial adhesion molecules, NF-κB, inhibitory subunit of NF-κBα (IκBα), protein kinase Cβ2 (PKCβ2), and phosphorylation of PKCβ2 (Ser660) were measured by Western blot. NF-κB activity was measured by electrophoretic mobility shift assay. PKC activity was measured with SignaTECT PKC assay system. Superoxide anion (O2.-) accumulation was measured with the reduction of ferricytochrome c assay. Human peripheral mononuclear cells were prepared with Histopaque-1077 solution.ResultsHigh glucose induced the expression of endothelial selectin (E-selectin), intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), and increased mononuclear-endothelial adhesion. High glucose induced O2.- accumulation, PKCβ2 phosphorylation and PKC activation. Further, high glucose decreased IκBα expression in cytoplasm, increased the translocation of NF-κB from cytoplasm to nuclear, and induced NF-κB activation. Importantly, we found these high glucose-mediated effects were attenuated by propofol pretreatment. Moreover, CGP53353, a selective PKCβ2 inhibitor, decreased high glucose-induced NF-κB activation, adhesion molecules expression, and mononuclear-endothelial adhesion.ConclusionPropofol, via decreasing O2.- accumulation, down-regulating PKCβ2 Ser660 phosphorylation and PKC as well as NF-κB activity, attenuated high glucose-induced endothelial adhesion molecules expression and mononuclear-endothelial adhesion.

Highlights

Hyperglycemia could induce oxidative stress, activate transcription factor nuclear factor kappa B (NF-κB), up-regulate expression of endothelial adhesion molecules, and lead to endothelial injury
15 mM glucose-induced endothelial adhesion molecules expression and its modulation by propofol In human umbilical vein endothelial cells (HUVECs), compared with 5 mM glucose treatment, high concentrations of glucose caused a marked up-regulation of adhesion molecules expression in a concentration- and time-dependent manner
We found that propofol pre-treatment could attenuate 15 mM glucose-induced adhesion molecules expression in a concentration-dependent manner

Summary

Introduction

Hyperglycemia could induce oxidative stress, activate transcription factor nuclear factor kappa B (NF-κB), up-regulate expression of endothelial adhesion molecules, and lead to endothelial injury. We examined whether and how propofol improved high glucose-induced up-regulation of endothelial adhesion molecules in human umbilical vein endothelial cells (HUVECs). Lee et al and Kwon et al reported that high glucose-induced up-regulation of endothelial adhesion molecules was alleviated by inhibiting ROS generation and NF-κB activity [8,9]. Chen J et al found propofol could suppress oxidative stress, NF-κB activation and mononuclear-endothelial adhesion in endothelial cells exposed to hydrogen peroxide [10]. We examined whether propofol improved high glucose-induced up-regulation of endothelial adhesion molecules and mononuclear-endothelial adhesion in human umbilical vein endothelial cells (HUVECs).

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