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Effects and Molecular Mechanism of L-Type Calcium Channel on Fluoride-Induced Kidney Injury

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Abstract

This study aimed to investigate the role and molecular mechanism of L-type calcium channel (LTCC) on fluoride exposure-induced kidney injury. Subchronic and chronic fluoride exposures were included in the experiment. Each part contained 140 ICR male mice. They were randomly divided into 7 groups: control group, high-fluoride group (NaF 30 mg/L), low-fluoride group (NaF 5 mg/L), high/low-fluoride + agonist (FPL64176) group, high/low-fluoride + inhibitor (nifedipine) group. One week before the end of fluoride exposure, each mouse in the fluoride exposure group was injected intraperitoneally with LTCC agonist (FPL64176) or inhibitor (nifedipine) (5 mg/kg day). The apoptosis of kidney cell was observed by TUNEL, and the protein expression levels of Cav1.2 and CaM, CaMKII, Bcl-2, and Bax were detected by Western blot. Compared with the control group, the protein expression levels of Cav1.2, CaM, and Bax significantly increased, and those of CaMKII and Bcl-2 significantly decreased, the ratio of Bax/Bcl-2 also significantly increased, and the number of apoptotic kidney cells significantly increased in the high/low-fluoride group and in the high/low-fluoride + agonist group. The above indicators and fluoride exposure concentrations showed in time- and dose-dependent changes. Compared with the high/low-fluoride + agonist group, the protein expression level of the molecular in the kidney cells above mentioned was significantly opposite and the number of apoptotic kidney cells significantly decreased in the high/low-fluoride + inhibitor group. In conclusion, LTCC mediates the kidney injury induced by fluoride exposure in mice. Fluoride exposure induced abnormal expression of the Cav1.2 protein, Ca2+ signal transduction pathway, and apoptosis-regulated proteins, which is one of the molecular mechanisms. Nifedipine may be a new and effective anti-fluoride drug.

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Funding

This research was sponsored by the National Natural Science Foundation of China (grant number: 81573101).

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Authors and Affiliations

  1. College of Chemistry and Life Science, Zhejiang Normal University, Jinhua, Zhejiang, 321004, People’s Republic of China

    Dandan Shao, Jiayong Zhang, Le Tang & Qiuli Yu

  2. College of Xing Zhi, Zhejiang Normal University, Jinhua, Zhejiang, 321004, People’s Republic of China

    Xiaoxiao Hu, Qin Ruan & Zigui Zhang

  3. College of Sports and Health Science, Zhejiang Normal University, Jinhua, Zhejiang, 321004, People’s Republic of China

    Wei Ouyang

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  1. Dandan Shao
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  2. Jiayong Zhang
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  3. Le Tang
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  4. Qiuli Yu
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Correspondence to Wei Ouyang or Zigui Zhang.

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Shao, D., Zhang, J., Tang, L. et al. Effects and Molecular Mechanism of L-Type Calcium Channel on Fluoride-Induced Kidney Injury. Biol Trace Elem Res 197, 213–223 (2020). https://doi.org/10.1007/s12011-019-01987-x

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  • DOI: https://doi.org/10.1007/s12011-019-01987-x

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