Involvement of both mitochondrial- and death receptor-dependent apoptotic pathways regulated by Bcl-2 family in sodium fluoride-induced apoptosis of the human gingival fibroblasts.
Sodium fluoride (NaF) has been shown to be cytotoxic and produces inflammatory responses in humans. However, the cellular mechanisms underlying the NaF-induced cytotoxicity in periodontal tissues are unclear. This study examined whether or not NaF induces apoptosis in human gingival fibroblasts (HGF), and its underlying mechanisms by monitoring various apoptosis-associated processes. NaF reduced the cell viability of HGF in a dose- and time-dependent manner. NaF increased TUNEL-positive cell and induced apoptosis with concomitant chromatin condensation and DNA fragmentation in HGF. In addition, NaF increased the level of cytochrome c released from the mitochondria into the cytosol, enhanced the caspase-9, -8 and -3 activities, the cleavage of poly (ADP-ribose) polymerase (PARP), and up-regulated the voltage-dependent anion channel (VDAC) 1. However, NaF did not affect the production of reactive oxygen species (ROS) which is a strong apoptotic inducer. Furthermore, NaF up-regulated the Fas-ligand (Fas-L), a ligand of death receptor. Bcl-2, a member of the anti-apoptotic Bcl-2 family, was down-regulated, whereas the expression of Bax, a member of the pro-apoptotic Bcl-2 family, was unaffected in the NaF-treated HGF. These results suggest that NaF induces apoptosis in HGF through both the mitochondria-mediated pathways regulated by the Bcl-2 family and death receptor-mediated pathway.
Lee
Jin-Ha
JH
Dental Science Research Institute, 2nd Stage of Brain Korea 21 for School of Dentistry, Chonnam National University, Gwang Ju 500-757, South Korea.
Jung
Ji-Yeon
JY
Jeong
Yeon-Jin
YJ
Park
Jae-Hong
JH
Yang
Kyu-Ho
KH
Choi
Nam-Ki
NK
Kim
Sun-Hun
SH
Kim
Won-Jae
WJ
D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D020169:Caspases / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002843:Chromatin / Q000187:drug effects / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D053222:Fas Ligand Protein / Q000235:genetics / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005881:Gingiva / Q000166:cytology; D006801:Humans; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D053218:Receptors, Death Domain / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012969:Sodium Fluoride / Q000494:pharmacology*; D013997:Time Factors; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D051025:bcl-Associated Death Protein / Q000378:metabolism
D002843:Chromatin; D053222:Fas Ligand Protein; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D053218:Receptors, Death Domain; D051028:bcl-2-Associated X Protein; D051025:bcl-Associated Death Protein; D012969:Sodium Fluoride; D045304:Cytochromes c; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D020169:Caspases