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: Maiko Suzuki, Megan L Sierant, Jerry V Antone, Eric T Everett, Gary M Whitford, John D Bartlett
• Journal: Connective tissue research (Connect Tissue Res) Vol. 55 Suppl 1 Pg. 25-8 (Aug 2014) ISSN: 1607-8438 [Electronic] England
• PMID: 25158175 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Dental Enamel Proteins
• Ion Channels
• Mitochondrial Proteins
• Phosphates
• Ucp2 protein, mouse
• Ucp2 protein, rat
• Uncoupling Protein 2
• enamel matrix proteins
• fluorophosphate
• Fluorides

Topics

• Animals
• Dental Enamel Proteins (metabolism)
• Enamel Organ (drug effects)
• Fluorides (pharmacology)
• Fluorosis, Dental (metabolism)
• Ion Channels (metabolism)
• Mice, Inbred C57BL
• Mitochondrial Proteins (metabolism)
• Phosphates (pharmacology)
• Rats, Sprague-Dawley
• Transcriptional Activation
• Uncoupling Protein 2
• Up-Regulation