1. NaF Activates MAPKs and Induces Apoptosis in Odontoblast-like Cells.
- Author
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Karube, H., Nishitai, G., Inageda, K., Kurosu, H., and Matsuoka, M.
- Subjects
SODIUM fluoride ,MITOGEN-activated protein kinases ,APOPTOSIS ,DENTAL research ,CELL death ,ORAL microbiology - Abstract
The cytotoxic effects of fluoride on odontoblasts are not clear. In this study, we examined whether NaF induces apoptosis in MDPC-23 odontoblast-like cells and the involvement of mitogen-activated protein kinase (MAPK) signaling pathways in NaF-induced apoptosis. MDPC-23 cells incubated with 5 mM NaF for 24 hrs exhibited caspase-3 activation, cleavage of poly(ADP-ribose) polymerase, DNA fragmentation, and an increase in cytoplasmic nucleosomes. Prior to the induction of apoptosis, all MAPKs examined were phosphorylated, but in a different manner. In contrast to the sustained phosphorylation of c-Jun NH
2 -terminal kinase (JNK) and p38, NaF exposure induced a biphasic phosphorylation of extracellular signal-regulated protein kinase (ERK). NaF-induced apoptosis was markedly suppressed by treatment with the JNK inhibitor, SP600125, and mildly suppressed by the MAPK/ERK kinase inhibitor, U0126. Inhibition of p38 activity did not protect cells from apoptosis. Thus, exposure to NaF induces apoptosis in odontoblast-like cells, depending on JNK and, less significantly, ERK pathways. Abbreviations: Ac-DEVD-MCA, Acetyl-Asp-Glu-Val-Asp ɑ(4-methyl-coumaryl-7-amide); DMSO, dimethyl sulfoxide; ERK, extracellular signal-regulated protein kinase; FBS, fetal bovine serum; JNK, c-Jun NH2 - terminal kinase; MAPKs, mitogen-activated protein kinases; MEK1/2, MAPK/ERK kinase; MK-2, MAPK-activated protein kinase-2; NaF, sodium fluoride; PARP, poly(ADP-ribose) polymerase; SD, standard deviation. [ABSTRACT FROM AUTHOR]- Published
- 2009
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