The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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Involvement of Bcl-2 Family and Caspases Cascade in Sodium Fluoride-Induced Apoptosis of Human Gingival Fibroblasts

  • Jung, Ji-Yeon (Dental Science Research Institute, School of Dentistry, 2nd Stage of Brain Korea 21 for School of Dentistry, Chonnam National University) ;
  • Park, Jae-Hong (Dental Science Research Institute, School of Dentistry, 2nd Stage of Brain Korea 21 for School of Dentistry, Chonnam National University) ;
  • Jeong, Yeon-Jin (Dental Science Research Institute, School of Dentistry, 2nd Stage of Brain Korea 21 for School of Dentistry, Chonnam National University) ;
  • Yang, Kyu-Ho (Dental Science Research Institute, School of Dentistry, 2nd Stage of Brain Korea 21 for School of Dentistry, Chonnam National University) ;
  • Choi, Nam-Ki (Dental Science Research Institute, School of Dentistry, 2nd Stage of Brain Korea 21 for School of Dentistry, Chonnam National University) ;
  • Kim, Sun-Hun (Dental Science Research Institute, School of Dentistry, 2nd Stage of Brain Korea 21 for School of Dentistry, Chonnam National University) ;
  • Kim, Won-Jae (Dental Science Research Institute, School of Dentistry, 2nd Stage of Brain Korea 21 for School of Dentistry, Chonnam National University)
  • Published : 2006.10.01
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Abstract

Sodium fluoride (NaF) has been shown to be cytotoxic and elicit inflammatory response in human. However, the cellular mechanisms underlying NaF-induced cytotoxicity in periodontal tissues have not yet been elucidated. This study is aimed to investigate the mechanisms of NaF-induced apoptosis in human gingival fibroblast (HGF). NaF decreased the cell viability of HGF in a dose- and time-dependent manner. NaF gave rise to apoptotic morphological changes including cell shrinkage, chromatin condensation, and DNA fragmentation. However, NaF did not affect the production of ROS. In addition, NaF augumented cytochrome c release from mitochondria into the cytosol, and enhanced caspase -9 and -3 activities., cleavage (85 kDa fragments) of poly (ADP-ribose) polymerase (PARP) and upregulation of voltage-dependent anion channel (VDAC) 1. These results demonstrated that NaF-induced apoptosis in HGF may be mediated with mitochondria. Furthermore, NaF elevated caspase-8 activity and upregulated Fas-ligand (Fas-L), suggesting involvement of death receptor mediated pathway in NaF-induced apoptosis. Expression of Bcl-2, an anti-apoptotic Bcl-2 family, was downregulated, whereas expression of Bax, a pro-apoptotic Bcl-2 family, was not affected in NaF-treated HGF. These results suggest that NaF induces apoptosis in HGF through both mitochondria- and death receptor-mediated pathway mediated by Bcl-2 family.

Keywords

References

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