Glutamine protects against oxidative stress injury through inhibiting the activation of PI3K/Akt signaling pathway in parkinsonian cell model

Environ Health Prev Med. 2019 Jan 5;24(1):4. doi: 10.1186/s12199-018-0757-5.

Abstract

Background: Parkinson's disease is a neurodegenerative disorder, and recent studies suggested that oxidative stress contributes to the degeneration of dopamine cell in Parkinson's disease. Glutamine also has a positive role in reducing oxidative stress damage. In this study, we hypothesized that glutamine offers protection against oxidative stress injury in 1-methyl-4-phenylpyridinium (MPP+)-induced Parkinson's disease cell model.

Methods: MPP+ was used to induce PD models in PC12 cells and classified into control, M0 (MPP+), G0 (glutamine), and M0+G0 groups. CCK-8 and AO/EB staining assays were used to examine cell proliferation and apoptosis, respectively. Western blotting was applied to examine the protein expression of PI3K, P-Akt, Akt, P-mTOR, and mTOR.

Results: We showed that glutamine suppressed cytotoxicity induced by MPP+ in PC12 cells. MPP+ decreased the superoxide dismutase and glutathione peroxidase activity and increased the malondialdehyde content, which were restored by glutamine. Moreover, MPP+ increased the expression of PI3K, P-Akt, Akt, P-mTOR, and mTOR, which were inhibited by glutamine. And the antioxidant capacity of glutamine on PC12 cells could be improved by LY294002 and inhibited by IGF-1.

Conclusion: These results suggest that glutamine strengthens the antioxidant capacity in PC12 cells induced by MPP+ through inhibiting the activation of the PI3K/Akt signaling pathway. The effects of glutamine should be investigated and the protective mechanism of glutamine in PD must be explored in future studies.

Keywords: Glutamine; Oxidative stress; PC12; PI3K/Akt; Parkinson’s disease.

Publication types

  • Comparative Study

MeSH terms

  • 1-Methyl-4-phenylpyridinium / administration & dosage
  • Analysis of Variance
  • Animals
  • Cell Culture Techniques
  • Disease Models, Animal
  • Glutamine / pharmacology*
  • Oxidative Stress / drug effects*
  • Parkinson Disease
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Protective Agents / pharmacology
  • Proto-Oncogene Proteins c-akt / metabolism
  • Rats

Substances

  • Protective Agents
  • Glutamine
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
  • 1-Methyl-4-phenylpyridinium