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

Title
Neuroprotective effects of Paeonia Lactiflora extract against cell death of dopaminergic SH-SY5Y cells is mediated by epigenetic modulation
Authors
Lee, GyuhwiJoo, Jong CheonChoi, Bo YoonLindroth, Anders M.Park, Soo JungPark, Yoon Jung
Ewha Authors
박윤정
SCOPUS Author ID
박윤정scopus
Issue Date
2016
Journal Title
BMC COMPLEMENTARY AND ALTERNATIVE MEDICINE
ISSN
1472-6882JCR Link
Citation
vol. 16
Keywords
Paeonia lactifloraHistone acetylationEpigeneticsMPP+-induced cell deathNeuroprotective effect
Publisher
BIOMED CENTRAL LTD
Indexed
SCIE; SCOPUS WOS scopus
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 similar to 200 mu g/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.
DOI
10.1186/s12906-016-1205-y
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신산업융합대학 > 식품영양학과 > Journal papers
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