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Neuroprotective Effects of Deuterium-Depleted Water (DDW) Against H2O2-Induced Oxidative Stress in Differentiated PC12 Cells Through the PI3K/Akt Signaling Pathway

Abstract

Oxidative stress plays an important role in the pathogenesis of neurodegenerative diseases, including Alzheimer’s disease and Parkinson’s disease. Induction of endogenous antioxidants to act against oxidative stress-mediated neuronal damage seems to be a reasonable strategy for delaying the progression of such diseases. In this study, we investigated the neuroprotective effect of deuterium-depleted water (DDW) against H2O2-induced oxidative stress in differentiated PC12 cells and the possible signaling pathways involved. The differentiated PC12 cell line was pretreated with DDW containing different concentrations (50–100 ppm) of deuterium and then treated with H2O2 to induce oxidative stress and neurotoxicity. We assessed cell survival, reactive oxygen species (ROS) generation, TUNEL assay, catalase (CAT), copper and zinc-containing superoxide dismutase (CuZn-SOD) and superoxide dismutase (SOD) activity and performed Western blot analysis to investigate the neuroprotective effect of DDW. The results indicated that DDW could attenuate H2O2-induced apoptosis, reduce ROS formation, and increase CAT, CuZn-SOD and SOD activity in H2O2-treated PC12 cells. Western blot analysis revealed that DDW treatment significantly increased the expression of p-Akt, Bcl-2 and GSK-3β. However, the protective effect of DDW on cell survival and the DDW-mediated increases in p-Akt, Bcl-2 and GSK-3β were abolished by pretreatment with the phosphatidylinositol-3-kinase (PI3K) inhibitor LY294002. In summary, DDW may protect differentiated PC12 cells against H2O2-induced oxidative stress through the PI3K/Akt signaling pathway.

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Acknowledgements

This work was supported by the Scientific Research Fund of Guangdong Medical University (No. 2018007) to Dr. Hui Fu, the Construct TCM Research Program of Guangdong (No. 20162080) to Dongyun Qin, the "Group-type" Special Support Project for Education Talents in Universities (Nos. G619080438 and 4SG19045G).

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Correspondence to Hui Fu.

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Wu, Y., Qin, D., Yang, H. et al. Neuroprotective Effects of Deuterium-Depleted Water (DDW) Against H2O2-Induced Oxidative Stress in Differentiated PC12 Cells Through the PI3K/Akt Signaling Pathway. Neurochem Res 45, 1034–1044 (2020). https://doi.org/10.1007/s11064-020-02978-4

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  • DOI: https://doi.org/10.1007/s11064-020-02978-4

Keywords

  • Deuterium-depleted water (DDW)
  • PC12 cells
  • Neuroprotective effect
  • Oxidative stress