Protocatechuic acid attenuates β‑secretase activity and okadaic acid‑induced autophagy via the Akt/GSK‑3β/MEF2D pathway in PC12 cells

  • Authors:
    • Liping Huang
    • Xiaoqin Zhong
    • Shaochen Qin
    • Minzhen Deng
  • View Affiliations

  • Published online on: December 30, 2019     https://doi.org/10.3892/mmr.2019.10905
  • Pages: 1328-1335
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Okadaic acid (OA) can be used to induce an Alzheimer's disease (AD) model characterized by tau hyperphosphorylation, the formation of neurofibrillary tangles formation and β‑amyloid (Aβ) deposition. Previous studies have shown that the upregulation of Beclin‑1‑dependent autophagy may contribute to the elimination of aggregated Aβ. However, the effects of protocatechuic acid (PA) on the levels of Aβ42, phosphorylated (p)‑tau and β‑secretase in OA‑induced cell injury are unclear, and little is known concerning the role of the PA signaling pathway in the regulation of autophagy. The present study aimed to determine whether PA protects cells from OA‑induced cytotoxicity via the regulation of Beclin‑1‑dependent autophagy and its regulatory signaling pathway. PC12 cells were treated with OA with or without PA for 24 h. Enzymatic assays were performed to measure p‑tau, Aβ42 and β‑secretase activity. Western blotting was performed to detect p‑Akt, p‑glycogen synthase kinase‑3β (p‑GSK‑3β), Akt, GSK‑3β, myocyte enhancer factor 2D (MEF2D) and Beclin‑1 protein expression levels. Immunofluorescence and immunocytochemistry were used to measure Beclin‑1 expression levels. The results from this study showed that PA could increase cell viability and significantly decrease the levels of Aβ42, p‑tau, β‑secretase and Beclin‑1. PA can also promote the expression of p‑Akt and MEF2D while suppressing the expression of p‑GSK‑3β. These results indicated that PA protects PC12 cells from OA‑induced cytotoxicity, and attenuates autophagy via regulation of the Akt/GSK‑3β/MEF2D pathway, therefore potentially contributing to the neuroprotective effects of PA against OA toxicity. These findings suggested that PA may have potential as a drug candidate in preventative AD therapy.
View Figures
View References

Related Articles

Journal Cover

March 2020
Volume 21 Issue 3

Print ISSN: 1791-2997
Online ISSN:1791-3004

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
APA
Huang, L., Zhong, X., Qin, S., & Deng, M. (2020). Protocatechuic acid attenuates β‑secretase activity and okadaic acid‑induced autophagy via the Akt/GSK‑3β/MEF2D pathway in PC12 cells. Molecular Medicine Reports, 21, 1328-1335. https://doi.org/10.3892/mmr.2019.10905
MLA
Huang, L., Zhong, X., Qin, S., Deng, M."Protocatechuic acid attenuates β‑secretase activity and okadaic acid‑induced autophagy via the Akt/GSK‑3β/MEF2D pathway in PC12 cells". Molecular Medicine Reports 21.3 (2020): 1328-1335.
Chicago
Huang, L., Zhong, X., Qin, S., Deng, M."Protocatechuic acid attenuates β‑secretase activity and okadaic acid‑induced autophagy via the Akt/GSK‑3β/MEF2D pathway in PC12 cells". Molecular Medicine Reports 21, no. 3 (2020): 1328-1335. https://doi.org/10.3892/mmr.2019.10905