title: N-acetyl cysteine mediates protection from 2-hydroxyethyl methacrylate induced apoptosis via nuclear factor kappa B-dependent and independent pathways: potential involvement of JNK.
abstract: The mechanisms by which resin based materials induce adverse effects in patients have not been completely elucidated. Here we show that 2-hydroxyethyl methacrylate (HEMA) induces apoptotic cell death in oral keratinocytes. Functional loss and cell death induced by HEMA was significantly inhibited in the presence of N-acetyl cysteine (NAC) treatment. NAC also prevented HEMA mediated decrease in vascular endothelial growth factor secretion. The protective effect of NAC was partly related to its ability to induce NF-kappaB in the cells, since HEMA mediated inhibition of nuclear NF-kappaB expression and function was significantly blocked in the presence of NAC treatment. Moreover, blocking of nuclear translocation of NF-kappaB in oral keratinocytes sensitized these cells to HEMA mediated apoptosis. In addition, since NAC was capable of rescuing close to 50% of NF-kappaB knockdown cells from HEMA mediated cell death, there is, therefore, an NF-kappaB independent pathway of protection from HEMA mediated cell death by NAC. NAC mediated prevention of HEMA induced cell death in NF-kappaB knockdown cells was correlated with a decreased induction of c-Jun N-terminal kinase (JNK) activity since NAC inhibited HEMA mediated increase in JNK levels. Furthermore, the addition of a pharmacologic JNK inhibitor to HEMA treated cells prevented cell death and restored NF-kappaB knockdown cell function significantly. Therefore, NAC protects oral keratinocytes from the toxic effects of HEMA through NF-kappaB dependent and independent pathways. Moreover, our data suggest the potential involvement of JNK pathway in NAC mediated protection.
authors.affiliation: Division of Oral Biology and Medicine, The Jane and Jerry Weintraub Center for Reconstructive Biotechnology, Dental Research Institute, UCLA School of Dentistry and Medicine, University of California, Los Angeles, California 90095, USA.
authors.forename: Avina
authors.initials: A
authors.lastname: Paranjpe
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Cacalano
authors.forename: Wyatt R
authors.initials: WR
authors.lastname: Hume
authors.forename: Anahid
authors.initials: A
authors.lastname: Jewett
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis / Q000235:genetics; D003764:Dental Materials / Q000633:toxicity*; D004789:Enzyme Activation / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D016166:Free Radical Scavengers / Q000494:pharmacology*; D018014:Gene Transfer Techniques; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000502:physiology*; D015603:Keratinocytes / Q000187:drug effects; D008156:Luciferases / Q000378:metabolism; D008689:Methacrylates / Q000633:toxicity*; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000502:physiology*; D012190:Retroviridae / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D016207:Cytokines; D003764:Dental Materials; D016166:Free Radical Scavengers; D008689:Methacrylates; D016328:NF-kappa B; C005044:hydroxyethyl methacrylate; D004247:DNA; D008156:Luciferases; D048031:JNK Mitogen-Activated Protein Kinases; D000111:Acetylcysteine