title: NF-kappaB protection against apoptosis induced by HEMA.
abstract: The cytotoxicity of dental monomers has been widely investigated, but the underlying mechanisms have not been elucidated. We studied the molecular mechanisms involved in cell death induced by HEMA. In human primary fibroblasts, HEMA induced a dose-dependent apoptosis that was confirmed by the activation of caspases-8, -9, and -3. We found an increase of reactive oxygen species (ROS) and NF-kappaB activation after HEMA exposure. Blocking of ROS production by anti-oxidants had no direct influence on apoptosis caused by HEMA, but inhibition of NF-kappaB increased the fraction of apoptotic cells. Accordingly, mouse embryonic fibroblasts (MEF) from p65-/- mice were more susceptible to HEMA-induced apoptosis than were wild-type controls. Our results indicate that exposure to HEMA triggers apoptosis and that this mechanism is not directly dependent upon redox signaling. Nevertheless, ROS induction by HEMA activates NF-kappaB, which exerts a protective role in counteracting apoptosis.
authors.affiliation: Department of Oral and Maxillofacial Sciences, University of Naples, Italy. gspagnuo@unina.it
authors.forename: G
authors.initials: G
authors.lastname: Spagnuolo
authors.forename: C
authors.initials: C
authors.lastname: Mauro
authors.forename: A
authors.initials: A
authors.lastname: Leonardi
authors.forename: M
authors.initials: M
authors.lastname: Santillo
authors.forename: R
authors.initials: R
authors.lastname: Paternò
authors.forename: H
authors.initials: H
authors.lastname: Schweikl
authors.forename: E V
authors.initials: EV
authors.lastname: Avvedimento
authors.forename: S
authors.initials: S
authors.lastname: Rengo
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D020169:Caspases / Q000378:metabolism; D002478:Cells, Cultured; D004591:Electrophoresis, Polyacrylamide Gel; D004789:Enzyme Activation; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D008689:Methacrylates / Q000633:toxicity*; D051379:Mice; D016328:NF-kappa B / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012867:Skin / Q000166:cytology
chemical_list: D008689:Methacrylates; D016328:NF-kappa B; D017382:Reactive Oxygen Species; C005044:hydroxyethyl methacrylate; D020169:Caspases