title: Hemeoxygenase-1 expression in response to arecoline-induced oxidative stress in human umbilical vein endothelial cells.
abstract: BACKGROUND
  Arecoline, the most abundant areca alkaloid, has been reported to stimulate reactive oxygen species (ROS) production in several cell types. Overproduction of ROS has been implicated in atherogenesis. Hemeoxygenase-1 (HO-1) has cytoprotective activities in vascular tissues. This study investigated the effect of arecoline on adhesion molecule expression and explored the role of HO-1 in this process.
  
  
  METHODS
  Human umbilical vein endothelial cells (HUVECs) were treated with arecoline, then ROS levels and the expression of adhesion molecules and HO-1 were analyzed and potential signaling pathways investigated.
  
  
  RESULTS
  After 2h of arecoline treatment, ROS production was stimulated and reached a maximum at 12h. Expression of the adhesion molecules ICAM and VCAM was also induced. Glutathione pretreatment completely blocked arecoline-stimulated ROS production and VCAM expression, but not ICAM expression. Arecoline also induced HO-1 expression and this effect was partly due by ROS stimulation. Inhibition of c-jun N-terminal kinase (JNK) by SP600125, p38 by SB 203580, or tyrosine kinase by genistein reduced arecoline-induced HO-1 expression. In contrast, inhibition of ERK (extracellular signal-related MAP kinase) by PD98059 had no effect. Transfection of HUVECs with the GFP/HO-1 gene, which resulted in a 5-fold increase in HO-1 activity, markedly, but not completely, inhibited the decrease in cell viability caused by arecoline.
  
  
  CONCLUSIONS
  This study demonstrates that, in HUVECs, arecoline stimulates ROS production and ICAM and VCAM expression. HO-1 expression is also upregulated through the ROS, tyrosine kinase, and MAPK (JNK and p38) signaling pathways.
authors: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
authors: Thu-Ching
authors: TC
authors: Hung
authors: Li-Wen
authors: LW
authors: Huang
authors: Shu-Jem
authors: SJ
authors: Su
authors: Bau-Shan
authors: BS
authors: Hsieh
authors: Hsiao-Ling
authors: HL
authors: Cheng
authors: Yu-Chen
authors: YC
authors: Hu
authors: Yen-Hui
authors: YH
authors: Chen
authors: Chi-Ching
authors: CC
authors: Hwang
authors: Kee-Lung
authors: KL
authors: Chang
mesh_terms: D001115:Arecoline / Q000494:pharmacology*; D015153:Blotting, Western; D002478:Cells, Cultured; D018679:Cholinergic Agonists / Q000494:pharmacology; D004247:DNA / Q000235:genetics*; D042783:Endothelial Cells / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D005786:Gene Expression Regulation; D051547:Heme Oxygenase-1 / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D007424:Intracellular Fluid / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D014471:Umbilical Veins / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology
chemical_list: D018679:Cholinergic Agonists; D017382:Reactive Oxygen Species; D001115:Arecoline; D004247:DNA; D051547:Heme Oxygenase-1