Abstract | OBJECTIVE: Our previous studies demonstrated both phytoestrogen α- zearalanol (α-ZAL) and estrogen is effective decrease Alzheimer's disease (AD)-like apoptotic neuron death, but α-ZAL showed significantly less side-effect on breast and endometrial tissue compared to estrogen, it suggested that α-ZAL can be used as a potential substitute for estrogen. However, the molecular mechanism by which α-ZAL prevents neuron damage remains unclear. Growing evidence suggests that endoplasmic reticulum (ER) stress plays an important role in the process of cell apoptosis in AD; in addition, our published data indicated that α-ZAL possessed the potential ability to stabilize ER function. We therefore hypothesized that ER-stress mechanism maybe involved in the antiapoptotic effect of α-ZAL in this study. METHODS: Primary rat hippocampal neurons have been cultured and subsequently followed exposed to β- peptide fragment 25-35(Aβ25-35) with or without α-ZAL pre-treatment, and then western blot and flow cytometry techniques has been used to evaluate the intracellular calcium balance, ER stress and apoptotic cell death. RESULTS: The results showed that Aβ25-35 treatment for 24h induced dramatic neuronal apoptosis, accompanied by an increase in calpain2 expression, a marker of intracellular calcium overload. On the other hand, ER stress sensitive hallmarks, glucose-regulated protein 78 ( GRP78), double-stranded RNA-dependent protein kinase (PKR)-like ER-resident kinase (PERK) and C/EBP homologous protein-10 (CHOP10) expressions were up-regulated after Aβ25-35 administration. Importantly, α-ZAL pre-treatment effectively attenuated above changes. CONCLUSION: These results demonstrated that α-ZAL protects cells against AD-like apoptosis and the effects at least partially by attenuating severely ER stress.
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Authors | Yilong Dong, Ruiqian Li, Aimei Jiang, Zhong Xu, Yanmei Wang |
Journal | Neuro endocrinology letters
(Neuro Endocrinol Lett)
Vol. 38
Issue 5
Pg. 353-359
(Oct 2017)
ISSN: 0172-780X [Print] Sweden |
PMID | 29106790
(Publication Type: Journal Article)
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Chemical References |
- Amyloid beta-Peptides
- Peptide Fragments
- Phytoestrogens
- amyloid beta-protein (25-35)
- zearalenol
- Zeranol
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Topics |
- Amyloid beta-Peptides
(pharmacology)
- Animals
- Apoptosis
(drug effects)
- Endoplasmic Reticulum Stress
(drug effects)
- Hippocampus
(drug effects, metabolism)
- Neurons
(drug effects, metabolism)
- Peptide Fragments
(pharmacology)
- Phytoestrogens
(pharmacology)
- Rats
- Zeranol
(analogs & derivatives, pharmacology)
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