title: Uncoupling protein-2 is an antioxidant that is up-regulated in the enamel organ of fluoride-treated rats.
abstract: Dental fluorosis is characterized by subsurface hypomineralization and retention of enamel matrix proteins. Fluoride (F(-)) exposure generates reactive oxygen species (ROS) that can cause endoplasmic reticulum (ER)-stress. We therefore screened oxidative stress arrays to identify genes regulated by F(-) exposure. Vitamin E is an antioxidant so we asked if a diet high in vitamin E would attenuate dental fluorosis. Maturation stage incisor enamel organs (EO) were harvested from F(-)-treated rats and mice were assessed to determine if vitamin E ameliorates dental fluorosis. Uncoupling protein-2 (Ucp2) was significantly up-regulated by F(-) (∼1.5 & 2.0 fold for the 50 or 100 ppm F(-) treatment groups, respectively). Immunohistochemical results on maturation stage rat incisors demonstrated that UCP2 protein levels increased with F(-) treatment. UCP2 down-regulates mitochondrial production of ROS, which decreases ATP production. Thus, in addition to reduced protein translation caused by ER-stress, a reduction in ATP production by UCP2 may contribute to the inability of ameloblasts to remove protein from the hardening enamel. Fluoride-treated mouse enamel had significantly higher quantitative fluorescence (QF) than the untreated controls. No significant QF difference was observed between control and vitamin E-enriched diets within a given F(-) treatment group. Therefore, a diet rich in vitamin E did not attenuate dental fluorosis. We have identified a novel oxidative stress response gene that is up-regulated in vivo by F(-) and activation of this gene may adversely affect ameloblast function.
authors.affiliation: Department of Mineralized Tissue Biology, The Forsyth Institute & Harvard School of Dental Medicine , Cambridge, MA , USA .
authors.forename: Maiko
authors.initials: M
authors.lastname: Suzuki
authors.forename: Megan L
authors.initials: ML
authors.lastname: Sierant
authors.forename: Jerry V
authors.initials: JV
authors.lastname: Antone
authors.forename: Eric T
authors.initials: ET
authors.lastname: Everett
authors.forename: Gary M
authors.initials: GM
authors.lastname: Whitford
authors.forename: John D
authors.initials: JD
authors.lastname: Bartlett
mesh_terms: D000818:Animals; D003746:Dental Enamel Proteins / Q000378:metabolism; D004658:Enamel Organ / Q000187:drug effects*; D005459:Fluorides / Q000494:pharmacology*; D009050:Fluorosis, Dental / Q000378:metabolism*; D007473:Ion Channels / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D024101:Mitochondrial Proteins / Q000378:metabolism*; D010710:Phosphates / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley; D015533:Transcriptional Activation; D000071246:Uncoupling Protein 2; D015854:Up-Regulation
chemical_list: D003746:Dental Enamel Proteins; D007473:Ion Channels; D024101:Mitochondrial Proteins; D010710:Phosphates; C000604390:Ucp2 protein, mouse; C000604391:Ucp2 protein, rat; D000071246:Uncoupling Protein 2; C109069:enamel matrix proteins; C012980:fluorophosphate; D005459:Fluorides
keywords: Enamel; UCP2; fluoride; fluorosis; oxidative stress; vitamin E