Regulation of protease-activated receptor-1 expression in human buccal fibroblasts stimulated with arecoline

Head Neck. 2013 Sep;35(9):1314-8. doi: 10.1002/hed.23130. Epub 2012 Sep 10.

Abstract

Background: The purpose of this study was to compare the major thrombin receptor protease-activated receptor-1 (PAR-1) expression in normal human buccal mucosa and oral submucous fibrosis (OSF) specimens and further explore the potential mechanisms that may lead to induce PAR-1 expression.

Methods: Thirty OSF and 10 normal buccal mucosa specimens were examined by immunohistochemistry. Buccal mucosal fibroblasts (BMFs) were challenged with arecoline by using Western blot analysis. N-acetyl-L-cysteine (NAC), LY294002, herbimycin A, NS-398, and PD98059 were added to find the possible regulatory mechanisms.

Results: PAR-1 expression was significantly higher in OSF specimens (p < .05). Arecoline was found to elevate PAR-1 expression in a dose-dependent and time-dependent manner (p < .05). The addition of NAC, LY294002, herbimycin A, NS398, and PD98059 markedly inhibited the arecoline-induced PAR-1 expression (p < .05).

Conclusion: PAR-1 expression is significantly upregulated in areca quid chewing-associated OSF. Arecoline-induced PAR-1 expression was downregulated by NAC, LY294002, herbimycin A, NS398, and PD98059.

Keywords: arecoline; buccal mucosal fibroblasts; oral submucous fibrosis; protease-activated receptor-1; regulatory mechanisms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcysteine / pharmacology
  • Arecoline / pharmacology*
  • Blotting, Western
  • Cell Culture Techniques
  • Cholinergic Agonists / pharmacology*
  • Chromones / pharmacology
  • Enzyme Inhibitors / pharmacology
  • Fibroblasts / drug effects
  • Fibroblasts / enzymology*
  • Flavonoids / pharmacology
  • Humans
  • Immunohistochemistry
  • Morpholines / pharmacology
  • Mouth Mucosa / cytology*
  • Nitrobenzenes / pharmacology
  • Oral Submucous Fibrosis / enzymology*
  • Receptor, PAR-1 / metabolism*
  • Rifabutin / analogs & derivatives
  • Rifabutin / pharmacology
  • Sulfonamides / pharmacology

Substances

  • Cholinergic Agonists
  • Chromones
  • Enzyme Inhibitors
  • Flavonoids
  • Morpholines
  • Nitrobenzenes
  • Receptor, PAR-1
  • Sulfonamides
  • N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide
  • Rifabutin
  • 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
  • Arecoline
  • herbimycin
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
  • Acetylcysteine