title: Propofol upregulates heme oxygenase-1 through activation of ERKs in human umbilical vein endothelial cells under oxidative stress conditions.
abstract: BACKGROUND
  Heme oxygenase-1 (HO-1) is an important cytoprotective agent. We examined the effect of propofol on the regulation of HO-1 expression and its activity in human umbilical vein endothelial cells (HUVECs) under oxidative stress conditions. We further assessed whether extracellular signal-regulated kinases (ERKs), cJun-N-terminal kinases (JNKs), and p38-mitogen-activated protein kinase mediate propofol-induced HO-1 expression.
  
  
  METHODS
  Hydrogen peroxide (100 μmol/L) was used to induce oxidative stress. HUVECs were treated with different concentrations (1025 and 50 μmol/L) of propofol for various periods of time. Finally, cells were pretreated with SB203580 (10 μmol/L), a p38-mitogen-activated protein kinase inhibitor; PD98059 (25 μmol/L), an ERKs inhibitor; SP600125 (10 μmol/L), a JNKs inhibitor; and ZnPPIX (10 μmol/L), an HO-1 activity inhibitor, followed by propofol incubation. Reverse transcriptase polymerase chain reaction was used to detect HO-1 mRNA expression. HO-1 activity was determined in microsomal fractions from HUVECs by monitoring the conversion of heme into bilirubin. HO-1 protein and phosphorylated ERKs were measured by western blot analysis. Cell apoptosis was detected using terminal transferase deoxyuridine triphosphate-biotin nick-end labeling.
  
  
  RESULTS
  Under oxidative stress conditions, HO-1 expression and activity were increased by propofol in a dose-dependent and time-dependent manner. PD98059, but not SB203580 or SP600125, effectively reduced propofol-induced HO-1 protein levels. The phosphorylation of ERKs was significantly increased by propofol, and this process was also inhibited by PD98059. Hydrogen peroxide-induced apoptosis in HUVECs was attenuated by propofol, which was partly reversed by ZnPPIX.
  
  
  CONCLUSIONS
  These findings show that, under oxidative stress conditions, propofol induces HO-1 expression in HUVECs and this effect is mediated, at least in part, via ERKs pathways.
authors: Department of Anesthesiology, Zhongshan Hospital, Shanghai, China.
authors: Chao
authors: C
authors: Liang
authors: Zhanggang
authors: Z
authors: Xue
authors: Hao
authors: H
authors: Wang
authors: Ping
authors: P
authors: Li