Equol pretreatment protection of SH-SY5Y cells against Aβ (25-35)-induced cytotoxicity and cell-cycle reentry via sustaining estrogen receptor alpha expression

Meng Chao Tsai, Shyh Hsiang Lin, Kiswatul Hidayah, Ching I. Lin

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

β-amyloid formation in the brain is one of the characteristics of Alzheimer’s disease. Exposure to this peptidemayresult in reentry into the cell cycle leading to cell death. The phytoestrogen equol has similar biological effects as estrogen without the side effects. This study investigated the possible mechanism of the neuron cell-protecting effect of equol during treatment with Aβ. SH-SY5Y neuroblastoma cells were treated with either 1 µM S-equol or 10 nM 17β-estradiol for 24 h prior to 1 µM Aβ (25-35) exposure. After 24 h exposure to Aβ (25-35), a significant reduction in cell survival and a reentry into the cell cycle process accompanied by increased levels of cyclin D1 were observed. The expressions of estrogen receptor alpha (ERff) and its coactivator, steroid receptor coactivator-1 (SRC-1), were also significantly downregulated by Aβ (25-35) in parallel with activated extracellular signal-regulated kinase (ERK)1/2. However, pretreatment of cells with S-equol or 17β-estradiol reversed these effects. Treatment with the ER antagonist, ICI-182,780 (1 µM), completely blocked the effects of S-equol and 17β-estradiol on cell viability, ERff, and ERK1/2 after Aβ (25-35) exposure. These data suggest that S-equol possesses a neuroprotective potential as it effectively antagonizes Aβ (25-35)-induced cell cytotoxicity and prevents cell cycle reentry in SH-SY5Y cells. The mechanism underlying S-equol neuroprotection might involve ERff-mediated pathways.

Original languageEnglish
Article number2356
JournalNutrients
Volume11
Issue number10
DOIs
Publication statusPublished - Oct 2019

Keywords

  • Alzheimer’s disease
  • Cell cycle
  • Estrogen receptor alpha
  • S-equol; 17β-estradiol
  • β-amyloid

ASJC Scopus subject areas

  • Food Science
  • Nutrition and Dietetics

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