title: Apoptosis induced by the monomers HEMA and TEGDMA involves formation of ROS and differential activation of the MAP-kinases p38, JNK and ERK.
abstract: OBJECTIVE
  Cytotoxic methacrylate monomers have been identified in aqueous extracts of freshly cured compomers. Some of these compounds, including HEMA and TEGDMA, induce apoptosis and necrosis in vitro. The aim of the present study was to elucidate possible signaling pathways involved in apoptosis following exposure to HEMA or TEGDMA in a salivary gland cell line.
  
  
  METHODS
  The cells were exposed to various concentrations of HEMA or TEGDMA. ROS formation was determined by dichlorofluorescein assay. Phosphorylated MAP-kinases ERK1/2, p38 and JNK, as well as specific caspases were identified by Western blotting. Apoptosis was assayed by fluorescence microscopy.
  
  
  RESULTS
  HEMA or TEGDMA exposure resulted in ROS formation and concentration-dependent apoptosis as well as phosphorylation of ERK. Phosphorylation of JNK and p38 was induced by HEMA. Selective inhibitors of ERK and JNK modified the apoptotic response after HEMA and TEGDMA exposure, whereas p38 inhibition modified the apoptotic response only after HEMA exposure. Vitamin C reduced HEMA-induced apoptosis.
  
  
  CONCLUSIONS
  ROS formation and differential MAP kinase activation appear to be involved in the apoptotic response following exposure to HEMA and TEGDMA.
authors.affiliation: NIOM-Nordic Institute of Dental Materials, PO Box 70, N-1305 Haslum, Norway. jts@niom.no
authors.forename: Jan T
authors.initials: JT
authors.lastname: Samuelsen
authors.forename: Jon E
authors.initials: JE
authors.lastname: Dahl
authors.forename: Stig
authors.initials: S
authors.lastname: Karlsson
authors.forename: Else
authors.initials: E
authors.lastname: Morisbak
authors.forename: Rune
authors.initials: R
authors.lastname: Becher
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001205:Ascorbic Acid / Q000494:pharmacology; D015153:Blotting, Western; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D003764:Dental Materials / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D005419:Flavonoids / Q000494:pharmacology; D005456:Fluorescent Dyes; D048670:MAP Kinase Kinase 4 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008689:Methacrylates / Q000494:pharmacology*; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011092:Polyethylene Glycols / Q000494:pharmacology*; D011109:Polymethacrylic Acids / Q000494:pharmacology*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D003764:Dental Materials; D005419:Flavonoids; D005456:Fluorescent Dyes; D008689:Methacrylates; D011109:Polymethacrylic Acids; D017382:Reactive Oxygen Species; C020946:triethylene glycol dimethacrylate; D011092:Polyethylene Glycols; C005044:hydroxyethyl methacrylate; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020169:Caspases; D001205:Ascorbic Acid; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one