title: Propofol protects against high glucose-induced endothelial adhesion molecules expression in human umbilical vein endothelial cells.
abstract: BACKGROUND
  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. 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).
  
  
  METHODS
  Protein expression of endothelial adhesion molecules, NF-κB, inhibitory subunit of NF-κBα (IκBα), protein kinase Cβ2 (PKCβ2), and phosphorylation of PKCβ2 (Ser(660)) 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 (O(2)(.-)) accumulation was measured with the reduction of ferricytochrome c assay. Human peripheral mononuclear cells were prepared with Histopaque-1077 solution.
  
  
  RESULTS
  High 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 O(2)(.-) 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.
  
  
  CONCLUSIONS
  Propofol, via decreasing O(2)(.-) accumulation, down-regulating PKCβ2 Ser(660) phosphorylation and PKC as well as NF-κB activity, attenuated high glucose-induced endothelial adhesion molecules expression and mononuclear-endothelial adhesion.
authors: Department of Anaesthesiology and Oncology, Shanghai Medical College, Fudan University Shanghai Cancer Centre, Shanghai, People's Republic of China.
authors: Minmin
authors: M
authors: Zhu
authors: Jiawei
authors: J
authors: Chen
authors: Hui
authors: H
authors: Jiang
authors: Changhong
authors: C
authors: Miao
mesh_terms: D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D005947:Glucose / Q000008:administration & dosage*; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D015742:Propofol / Q000494:pharmacology*; D020011:Protective Agents / Q000494:pharmacology
chemical_list: D015815:Cell Adhesion Molecules; D020011:Protective Agents; D005947:Glucose; D015742:Propofol