title: Regulation of extracellular signal-regulated protein kinase signaling in human osteosarcoma cells stimulated with nicotine.
abstract: BACKGROUND
  Cigarette smoking is a major risk factor in the development and further progression of periodontal diseases. Currently, there is limited information on the regulation of mitogen-activated protein kinases (MAPK) expression in smoking-associated periodontal disease.
  
  
  OBJECTIVE
  The aim of the present study was to investigate the effects of nicotine on the expression of MAPKs in human osteosarcoma cell line U2OS cells. Furthermore, various pharmacological agents were added to search the possible regulation mechanisms on nicotine-induced MAPKs expression.
  
  
  METHODS
  Cytotoxicity and western blot assays were used to investigate the effects of U2OS cells exposed to nicotine. In addition, various pharmacological agents [NS-398, dexamethasome, 2-oxothiazolidine-4-carboxylic acid (OTZ), herbimycin A, and curcumin] were added to test how they modulated the effects of nicotine-induced MAPKs expression.
  
  
  RESULTS
  Concentrations of nicotine higher than 5 mm demonstrated cytotoxicity to U2OS cells (p<0.05). A nicotine concentration of 5 mm was found to induce extracellular signal-regulated kinase (ERK) phosphorylation in a time-dependent manner (p<0.05). In addition, amounts of ERK protein were unaffected by nicotine during the same time interval. By contrast, nicotine has no effect on either c-Jun N-terminal kinase (JNK) or p38, respectively. In addition, NS-398, dexamethasone, OTZ, herbimycin A, and curcumin were found to inhibit the nicotine-induced ERK expression (p<0.05).
  
  
  CONCLUSIONS
  The activation of ERK expression by nicotine suggests a potential role for nicotine in the pathogenesis of cigarette smoking-associated periodontal disease. In addition, nicotine-induced ERK expression was down-regulated by NS-398, dexamethasone, OTZ, herbimycin A, and curcumin.
authors.affiliation: Institute of Biochemistry, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Chih-Yang
authors.initials: CY
authors.lastname: Huang
authors.forename: Juen-Hau
authors.initials: JH
authors.lastname: Chen
authors.forename: Chung-Hung
authors.initials: CH
authors.lastname: Tsai
authors.forename: Wei-Wen
authors.initials: WW
authors.lastname: Kuo
authors.forename: Jer-Yuh
authors.initials: JY
authors.lastname: Liu
authors.forename: Yu-Chao
authors.initials: YC
authors.lastname: Chang
mesh_terms: D015153:Blotting, Western / Q000379:methods; D045744:Cell Line, Tumor; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009538:Nicotine / Q000633:toxicity*; D012516:Osteosarcoma; D012907:Smoking / Q000009:adverse effects; D018675:Toxicity Tests
chemical_list: D009538:Nicotine; D048049:Extracellular Signal-Regulated MAP Kinases; D020928:Mitogen-Activated Protein Kinases