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Epigallocatechin Gallate Attenuates β-Amyloid Generation and Oxidative Stress Involvement of PPARγ in N2a/APP695 Cells

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Abstract

The accumulation of β-amyloid (Aβ) peptide plaques is a major pathogenic event in Alzheimer’s disease (AD). Aβ is a cleaved fragment of APP via BACE1, which is the rate-limiting enzyme in APP processing and Aβ generation. Nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ) is considered to be a potential target for AD treatment, because of its potent antioxidant and inhibitory effects on Aβ production by negatively regulating BACE1. Epigallocatechin gallate (EGCG), a highly active catechin found in green tea, is known to enhance metabolic activity and cognitive ability in the mice model of AD. To investigate whether the therapeutic effect of EGCG is related to the PPARγ pathway, we analysed the alterations in the intracellular molecular expression of PPARγ after EGCG treatment in the N2a/APP695 cell line. In this study, we observed that EGCG attenuated Aβ generation in N2a/APP695 cells, such as the PPARγ agonist, pioglitazone, by suppressing the transcription and translation of BACE1 and that its effect was attenuated by the PPARγ inhibitor, GW9662. Intriguingly, EGCG significantly reinforced the activity of PPARγ by promoting its mRNA and protein expressions in N2a/APP695 cells. Moreover, EGCG also decreased the expression of pro-apoptotic proteins (Bax, caspase-3), reduced the activity of the anti-inflammatory agent NF-κB and inhibited the oxidative stress by decreasing the levels of ROS and MDA and increasing the expression of MnSOD. Co-administration of GW9662 also significantly decreased the EGCG-mediated neuroprotective effect evidenced by the increase in oxidative stress and inflammatory markers. The therapeutic efficacy of EGCG in AD may be derived from the up-regulation of PPARγ mRNA and protein expressions.

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Abbreviations

AD:

Alzheimer’s disease

Aβ:

β-Amyloid peptides

APP:

Amyloid precursor protein

BACE1:

β-Site amyloid precursor protein-cleaving enzyme 1

PPARγ:

Peroxisome proliferator activated receptor-γ

PIG:

Pioglitazone

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Acknowledgements

This work was supported by Grants from the National Natural Science Foundation of China (No. 81303013).

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Authors and Affiliations

  1. Department of Neurology, The Shandong Province Qianfoshan Hospital, Jinan, 250000, China

    Zhao-Xu Zhang & Yan-Bing Li

  2. Division of Medical Quality Control, The Shandong Province Qianfoshan Hospital, Jinan, 250000, China

    Rui-Ping Zhao

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  1. Zhao-Xu Zhang
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  2. Yan-Bing Li
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Correspondence to Zhao-Xu Zhang or Rui-Ping Zhao.

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Zhang, ZX., Li, YB. & Zhao, RP. Epigallocatechin Gallate Attenuates β-Amyloid Generation and Oxidative Stress Involvement of PPARγ in N2a/APP695 Cells. Neurochem Res 42, 468–480 (2017). https://doi.org/10.1007/s11064-016-2093-8

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  • DOI: https://doi.org/10.1007/s11064-016-2093-8

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