Possible link between glycolysis and apoptosis induced by sodium fluoride.
Fluoride has been used to prevent caries in the dentition, but the possible underlying mechanisms of cytotoxicity induction by this compound are still unclear. Since fluoride is known as an inhibitor of glycolytic enzymes, we investigated the possible connection between NaF-induced apoptosis and glycolysis in human promyelocytic leukemia HL-60 cells. NaF-induced apoptotic cell death is characterized by caspase activation, internucleosomal DNA fragmentation, loss of mitochondrial membrane potential, and production of apoptotic bodies. Higher activation of caspases-3 and -9, as compared with that of caspase-8, suggested the involvement of an extrinsic pathway. Utilization of glucose was nearly halted by NaF, whereas that of glutamine was rather enhanced. NaF enhanced the expression of Bad protein, but not that of Bcl-2 and Bax proteins, and reduced HIF-1alpha mRNA expression. Analysis of these data suggests a possible link between glycolysis and apoptosis.
Otsuki
S
S
Department of Dental Pharmacology, Meikai Pharmaco-Medical Laboratory, Meikai University School of Dentistry, Sakado, Saitama 350-0283, Japan. sumoh@sf7.so-net.ne.jp
Morshed
S R M
SR
Chowdhury
S A
SA
Takayama
F
F
Satoh
T
T
Hashimoto
K
K
Sugiyama
K
K
Amano
O
O
Yasui
T
T
Yokote
Y
Y
Akahane
K
K
Sakagami
H
H
D017209:Apoptosis / Q000187:drug effects*; D002327:Cariostatic Agents / Q000494:pharmacology*; D020169:Caspases / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D005973:Glutamine / Q000378:metabolism; D006019:Glycolysis / Q000187:drug effects*; D018922:HL-60 Cells; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D012969:Sodium Fluoride / Q000494:pharmacology*; D018709:Statistics, Nonparametric; D051025:bcl-Associated Death Protein / Q000187:drug effects* / Q000378:metabolism
D002327:Cariostatic Agents; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D051025:bcl-Associated Death Protein; D005973:Glutamine; D012969:Sodium Fluoride; D020169:Caspases; D005947:Glucose