title: Negative regulation of NaF-induced apoptosis by Bad-CAII complex.
abstract: Fluoride is used to prevent caries in dentistry. However, its mechanism of cytotoxicity induction is unclear. This study was undertaken to determine whether sodium fluoride (NaF) induces apoptosis in human oral cells and if so, whether Bad protein is involved in the process. NaF showed higher cytotoxicity and apoptosis-inducing activity against human oral squamous cell carcinoma cells (HSC-2) than against human gingival fibroblasts (HGF). Western blot analysis showed that NaF enhanced the expression and dephosphorylation of Bad protein. This study demonstrates for the first time that Bad protein forms a complex with carbonic anhydrase II (CAII), and NaF stimulates the detachment of CAII from the Bad-CAII complex and the replacement by the formation of Bad-Bcl-2 complex. Knockdown of Bad and CAII mRNA by siRNA inhibited and enhanced the NaF-induced caspase activation, respectively. The present study suggests that CAII negatively regulates the NaF-induced apoptosis by forming a complex with Bad.
authors.affiliation: Division of Pharmacology, Meikai University School of Dentistry, Sakado, Saitama 350-0283, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Otsuki
authors.forename: K
authors.initials: K
authors.lastname: Sugiyama
authors.forename: O
authors.initials: O
authors.lastname: Amano
authors.forename: T
authors.initials: T
authors.lastname: Yasui
authors.forename: H
authors.initials: H
authors.lastname: Sakagami
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D024402:Carbonic Anhydrase II / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D045744:Cell Line, Tumor; D006801:Humans; D012969:Sodium Fluoride / Q000633:toxicity*; D051025:bcl-Associated Death Protein / Q000378:metabolism*
chemical_list: C494819:BAD protein, human; D051025:bcl-Associated Death Protein; D012969:Sodium Fluoride; D053148:Caspase 3; D053179:Caspase 7; D024402:Carbonic Anhydrase II