Abstract

Objective: To explore the role of mitochondrial biogenesis and the neuroprotective mechanism of resveratrol in fluoride neurotoxicity. Methods: SH-SY5Y cells in exponential phase were treated with different concentrations (20, 40, 60 mg/L) of sodium fluoride (NaF) for 24 h. Co-treatment with 60 mg/L NaF, 20 μmol/L resveratrol (RSV) was administrated in the resveratrol intervene trial. Western blotting was used to determine the expression levels of mitochondrial biogenesis key regulating factor of peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α) , nuclear respiratory factor 1 (NRF1) and mitochondrial transcription factor A (TFAM) in SH-SY5Y cells. The mRNA levels of PGC-1α, NRF1 and TFAM were determined by Quantitative Real-time PCR in SH-SY5Y cells, as well as the relative mitochondrial DNA (mtDNA) contents and mRNA expression of mitochondrial respiratory chain complexes subunit CO1 and ATP8. Flow cytometry was used to determine mitochondrial membrane potential in SH-SY5Y cells. Results: Both the protein and mRNA levels of PGC-1α, NRF1 and TFAM were decresed after 60 mg/L NaF treatment in SH-SY5Y cells (P<0.05) . The relative mtDNA contents and mRNA expression of complexes subunit CO1 and ATP8 were also significantly decreased compared with control (P<0.05) . Mitochondrial membrane potential were also significantly decreased after 60 mg/L NaF treatment in SH-SY5Y cells (P<0.05) . Compared with 60 mg/L NaF group, the protein and mRNA levels of PGC-1α, NRF1 and TFAM in 20 μmol/L RSV+60 mg/L NaF group were significantly increased (P<0.05) . The relative mtDNA contents, mitochondrial membrane potential and mRNA levels of complexes subunit CO1 and ATP8 in 20 μmol/L RSV+60 mg/L NaF group were also significantly higher than that in 60 mg/L NaF group (P<0.05) . Conclusion: Resveratrol may alleviate the fluoride-induced mitochondrial biogenesis dysfunction in SH-SY5Y cells.

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