Sirt1 overexpression suppresses fluoride-induced p53 acetylation to alleviate fluoride toxicity in ameloblasts responsible for enamel formation.

ABSTRACT: Low-dose fluoride is an effective caries prophylactic, but high-dose fluoride is an environmental health hazard that causes skeletal and dental fluorosis. Treatments to prevent fluorosis and the molecular pathways responsive to fluoride exposure remain to be elucidated. Previously we showed that fluoride activates SIRT1 as an adaptive response to protect cells. Here, we demonstrate that fluoride induced p53 acetylation (Ac-p53) [Lys379], which is a SIRT1 deacetylation target, in ameloblast-derived LS8 cells in vitro and in enamel organ in vivo. Here we assessed SIRT1 function on fluoride-induced Ac-p53 formation using CRISPR/Cas9-mediated Sirt1 knockout (LS8^Sirt/KO) cells or CRISPR/dCas9/SAM-mediated Sirt1 overexpressing (LS8^Sirt1/over) cells. NaF (5 mM) induced Ac-p5

SUBMITTER: Suzuki M 

PROVIDER: S-EPMC6667832 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature