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Published in: BMC Complementary Medicine and Therapies 1/2016

Open Access 01-12-2016 | Research article

Neuroprotective effects of Paeonia Lactiflora extract against cell death of dopaminergic SH-SY5Y cells is mediated by epigenetic modulation

Authors: Gyuhwi Lee, Jong Cheon Joo, Bo Yoon Choi, Anders M. Lindroth, Soo Jung Park, Yoon Jung Park

Published in: BMC Complementary Medicine and Therapies | Issue 1/2016

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Abstract

Background

The Paeonia lactiflora extract (PLE) has been reported to have neuroprotective effect against neurodegeneration that are induced by cellular stress such as oxidative stress. Its underlying mechanisms, however, remain unclear. In latest decades, emerging evidence has suggested that epigenetic mechanisms play a key role in gene regulation in response to the cellular stress. We investigated whether epigenetic modulation was involved in neuronal cell death by the neurotoxicant, 1-Methyl-4-phenylpyridinium (MPP+), and the neuroprotective effect of PLE.

Methods

Differentiated SH-SY5Y, which is a well-established dopaminergic cell line model, was treated with 0 ~ 200 μg/ml PLE for 4 h prior to MPP+ treatment. The effect of PLE on cell viability was determined by MTT assays. Gene expression levels of oxidative stress responsive genes, such as Heme oxygenase 1 (HMOX1), and histone modifiers, such as histone acetyltransferases (HATs) and deacetylases (HDACs) were measured by quantitative RT PCR. In order to investigate the changes in epigenetic modifications, the acetylated lysine 9 (H3K9ac) and lysine 27 (H3K27ac) of Histone H3 were measured by western blot using histones extracted from the cells.

Results

MPP+-induced cell death in SH-SY5Y cells was significantly reduced by PLE pretreatment in a dose-dependent manner, indicating the potent neuroprotective effects of PLE. It was accompanied by induced expression of HMOX1. MPP+ treatment increased the expression of HATs and consistently increased H3K9ac and H3K27ac of Histone H3. PLE pretreatment impeded the changes in H3K9ac and H3K27ac, coincided with increased expression of HDAC5 without changes in HAT expression.

Conclusions

The results suggested that MPP+-induced cell death in the dopaminergic SH-SY5Y cells was related with transcriptional induction of HATs and increased histone H3 acetylation and that PLE might prevent the cells from MPP+-induced cell death via tempering histone H3 acetylation.
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Metadata
Title
Neuroprotective effects of Paeonia Lactiflora extract against cell death of dopaminergic SH-SY5Y cells is mediated by epigenetic modulation
Authors
Gyuhwi Lee
Jong Cheon Joo
Bo Yoon Choi
Anders M. Lindroth
Soo Jung Park
Yoon Jung Park
Publication date
01-12-2016
Publisher
BioMed Central
Published in
BMC Complementary Medicine and Therapies / Issue 1/2016
Electronic ISSN: 2662-7671
DOI
https://doi.org/10.1186/s12906-016-1205-y

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