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Article

α-lipoic acid exerts neuroprotective effects on neuronal cells by upregulating the expression of PCNA via the P53 pathway in neurodegenerative conditions

  • Authors:
    • Da‑Wei Li
    • Ying‑Di Wang
    • Shi‑Yao Zhou
    • Wen‑Ping Sun
  • View Affiliations / Copyright

    Affiliations: Department of Neurology, Affiliated Hospital of Beihua University, Jilin, Jilin 132011, P.R. China, Department of Urinary Surgery, Tumor Hospital of Jilin, Changchun, Jilin 130021, P.R. China, Department of Clinical Medicine, Jilin University, Changchun, Jilin 130021, P.R. China
  • Pages: 4360-4366
    |
    Published online on: September 20, 2016
       https://doi.org/10.3892/mmr.2016.5754
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Abstract

Oxidative stress appears to be a central event responsible for the degeneration of dopaminergic neurons in Parkinson's disease (PD). 1-methyl-4‑phenyl-1,2,3,6-tetrahydropyridine or its toxic metabolite 1‑methyl‑4‑phenylpyridinium (MPP+) are classical widely‑used pharmacological and toxic agents to model PD; they cause the production of reactive oxygen species by inhibiting mitochondrial complex I, leading to DNA oxidative damage and subsequent neuronal death. Previous findings have suggested that proliferating cell nuclear antigen (PCNA), a critical regulatory protein for DNA repair, is involved in dopaminergic neuron damage in the MPP+‑induced PD model. The naturally occurring dithiol compound, α‑lipoic acid (ALA) has been reported to provide neuroprotection in in vitro models of PD. The molecular mechanism by which ALA reduces neuronal death in PD remains to be fully elucidated. The present study aimed to analyze the ability of ALA to protect neuronal PC12 cells from the toxicity induced by MPP+, and the molecular mechanism underlying these actions using MTT and lactate dehydrogenase cytotoxicity assays, Hoechst 33258 staining and western blot analysis. The results demonstrated that ALA efficiently increased the production of PCNA in MPP+‑treated PC12 cells. Accordingly, ALA treatment attenuated MPP+‑induced toxicity in the PC12 cells, and reduced cell apoptosis. The increase in the expression levels of PCNA by ALA in the MPP+‑treated PC12 cells appeared to be mediated by repression of the p53 protein, as the expression of p53 was increased by MPP+‑treatment and reduced by ALA. Taken together, these results indicated that ALA protected dopaminergic neurons against MPP+‑induced neurotoxicity through its ability to upregulate the DNA repair protein, PCNA, via the P53 pathway.
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Copy and paste a formatted citation
Spandidos Publications style
Li DW, Wang YD, Zhou SY and Sun WP: α-lipoic acid exerts neuroprotective effects on neuronal cells by upregulating the expression of PCNA via the P53 pathway in neurodegenerative conditions. Mol Med Rep 14: 4360-4366, 2016.
APA
Li, D., Wang, Y., Zhou, S., & Sun, W. (2016). α-lipoic acid exerts neuroprotective effects on neuronal cells by upregulating the expression of PCNA via the P53 pathway in neurodegenerative conditions. Molecular Medicine Reports, 14, 4360-4366. https://doi.org/10.3892/mmr.2016.5754
MLA
Li, D., Wang, Y., Zhou, S., Sun, W."α-lipoic acid exerts neuroprotective effects on neuronal cells by upregulating the expression of PCNA via the P53 pathway in neurodegenerative conditions". Molecular Medicine Reports 14.5 (2016): 4360-4366.
Chicago
Li, D., Wang, Y., Zhou, S., Sun, W."α-lipoic acid exerts neuroprotective effects on neuronal cells by upregulating the expression of PCNA via the P53 pathway in neurodegenerative conditions". Molecular Medicine Reports 14, no. 5 (2016): 4360-4366. https://doi.org/10.3892/mmr.2016.5754
Copy and paste a formatted citation
x
Spandidos Publications style
Li DW, Wang YD, Zhou SY and Sun WP: α-lipoic acid exerts neuroprotective effects on neuronal cells by upregulating the expression of PCNA via the P53 pathway in neurodegenerative conditions. Mol Med Rep 14: 4360-4366, 2016.
APA
Li, D., Wang, Y., Zhou, S., & Sun, W. (2016). α-lipoic acid exerts neuroprotective effects on neuronal cells by upregulating the expression of PCNA via the P53 pathway in neurodegenerative conditions. Molecular Medicine Reports, 14, 4360-4366. https://doi.org/10.3892/mmr.2016.5754
MLA
Li, D., Wang, Y., Zhou, S., Sun, W."α-lipoic acid exerts neuroprotective effects on neuronal cells by upregulating the expression of PCNA via the P53 pathway in neurodegenerative conditions". Molecular Medicine Reports 14.5 (2016): 4360-4366.
Chicago
Li, D., Wang, Y., Zhou, S., Sun, W."α-lipoic acid exerts neuroprotective effects on neuronal cells by upregulating the expression of PCNA via the P53 pathway in neurodegenerative conditions". Molecular Medicine Reports 14, no. 5 (2016): 4360-4366. https://doi.org/10.3892/mmr.2016.5754
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