Biological Trace Element Research

, Volume 185, Issue 2, pp 440–447 | Cite as

Mitochondria-Mediated Pathway Regulates C2C12 Cell Apoptosis Induced by Fluoride

  • Pan-pan Tan
  • Bian-hua Zhou
  • Wen-peng Zhao
  • Liu-shu Jia
  • Jing Liu
  • Hong-wei Wang


This study was designed to investigate the mechanisms of excessive fluoride-induced apoptosis via mitochondria-mediated pathway in skeletal muscle cells (C2C12 cells). C2C12 cells were cultured with the fluoride concentrations (0, 1, and 2.5 mmol/L) for 48 h. The morphology and ultrastructural changes of C2C12 cells were observed using a light microscope and transmission electron microscope (TEM). The protein expression levels of apoptosis factors, including Bax, Bcl-2, cytochrome c (Cyt c), caspase-3, and caspase-9, were measured using real-time polymerase chain reaction (real-time PCR) and immunocytofluorescence. The morphology and ultrastructure of C2C12 cells were seriously damaged by fluoride at 1 and 2.5 mmol/L doses, including swollen mitochondria, vacuolization, ridge breakage, and disappearance of the nuclear membrane. Simultaneously, compared with the control group, the expression levels of Bax, Bcl-2, Cyt c, caspase-3, and caspase-9 were up-regulated after fluoride treatment. Excessive fluoride damages the ultrastructure in mitochondria, leading to the release of Cyt c from the mitochondria to cytoplasm in C2C12 cells; thereby, activated caspases cascade apoptosis process through a mitochondria-mediated pathway.


Fluoride Apoptosis Mitochondria Caspase C2C12 cells 



This work is sponsored by the National Natural Science Foundation of China (grant no. 31201963) and Youth Backbone Teachers Project in Henan Province Department of Education, China (grant no. 2016GGJS-061).


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Henan Provincial Open Laboratory of Key Disciplines, Environment and Animal Products Safety, College of Animal Science and TechnologyHenan University of Science and TechnologyLuoyangPeople’s Republic of China

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