Vitamin C Attenuates Sodium Fluoride-Induced Mitochondrial Oxidative Stress and Apoptosis via Sirt1-SOD2 Pathway in F9 Cells

  • Wei Peng
  • Shangrong Xu
  • Jun ZhangEmail author
  • Yong ZhangEmail author


Increasing evidence has suggested an important role played by reactive oxygen species (ROS) in the pathogenesis of fluorosis. Accumulating evidence demonstrates that vitamin C administration ameliorate sodium fluoride (NaF)-induced oxidative stress. However, the potentially beneficial effects of vitamin C against NaF-induced cytotoxicity and the underlying molecular mechanisms of this protection are not fully understood. Here, we found that NaF stimulated cytotoxicity, increased mitochondrial reactive oxygen species (mROS) production, and induced apoptosis in F9 embryonic carcinoma cells. Consistent with this finding, NaF exposure was associated with decreased Sirtuin 1 (Sirt1) protein expression, thus promoted the acetylation of manganese superoxide dismutase (SOD2), a key enzyme involved in regulating mROS production. However, all NaF-induced mitochondrial oxidative injuries were efficiently ameliorated by overexpression of Sirt1 or incubation with Mito-TEMPO (a SOD2 mimetic). Moreover, pretreatment with vitamin C enhanced the expression of Sirt1 and decreased NaF-induced mitochondrial oxidative stress and apoptosis. Knockdown of Sirt1 blocked the vitamin C-mediated reduction in mROS and apoptosis via inhibiting Sirt1-SOD2 signaling. Importantly, sodium-dependent vitamin C transporter 2 (SVCT-2) siRNA was found to partially block the ability of vitamin C to promote Sirt1/SOD2 signaling. In summary, our data indicate that Sirt1 plays a pivotal role in the ability of vitamin C to stimulate SOD2 activity and attenuate mitochondrial oxidative stress, which partially through vitamin C receptor in NaF-induced F9 cells injury.


NaF Vitamin C F9 cells Sirt1 SOD2 SVCT-2 



Sodium fluoride


Reactive oxygen species


Mitochondrial reactive oxygen species


Sirtuin 1


Manganese superoxide dismutase


Sodium-dependent vitamin C transporter 2


Glucose transporter 1


Bcl2 associated X protein


B cell CLL/lymphoma 2


Cytochrome C oxidase subunit IV isoform 1


Glyceraldehyde-3-phosphate dehydrogenase




Coimmunoprecipitation pull-down


Mitochondrial membrane potential


Funding Information

This work was supported by the National Natural Science Foundation of China (No. 31702205) and Natural Science Basic Research Plan in Shaanxi Province of China (No. 2017JQ3028).

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflicts of interest.

Supplementary material

12011_2018_1599_MOESM1_ESM.doc (329 kb)
ESM 1 (DOC 329 kb)


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Copyright information

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

Authors and Affiliations

  1. 1.College of Veterinary MedicineNorthwest A&F UniversityYanglingChina
  2. 2.Key Laboratory of Animal Biotechnology, Ministry of AgricultureNorthwest A&F UniversityYanglingChina
  3. 3.Institute of Veterinary MedicineQinghai Academy of Animal Science and Veterinary MedicineXiningChina

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