title: Neuroprotective effects of Paeonia Lactiflora extract against cell death of dopaminergic SH-SY5Y cells is mediated by epigenetic modulation.
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.
authors.affiliation: Department of Nutritional Science and Food Management, College of Science and Industry Convergence, Ewha Womans University, Seodaemoon-gu, Seoul, 03760, Republic of Korea.
authors.forename: Gyuhwi
authors.initials: G
authors.lastname: Lee
authors.affiliation: Department of Sasang Constitutional Medicine, College of Korean Medicine, Wonkwang University, Iksan, 54538, Republic of Korea.
authors.forename: Jong Cheon
authors.initials: JC
authors.lastname: Joo
authors.affiliation: Department of Nutritional Science and Food Management, College of Science and Industry Convergence, Ewha Womans University, Seodaemoon-gu, Seoul, 03760, Republic of Korea.
authors.forename: Bo Yoon
authors.initials: BY
authors.lastname: Choi
authors.affiliation: Department of System Cancer Science, Graduate School of Cancer Science and Policy, National Cancer Center, Ilsandong-gu, Goyang, 10408, Republic of Korea.
authors.forename: Anders M
authors.initials: AM
authors.lastname: Lindroth
authors.affiliation: Department of Sasang Constitutional Medicine, College of Korean Medicine, Sangji University, Wonju, 26339, Republic of Korea. sjpark@sangji.ac.kr.
authors.forename: Soo Jung
authors.initials: SJ
authors.lastname: Park
authors.affiliation: Department of Nutritional Science and Food Management, College of Science and Industry Convergence, Ewha Womans University, Seodaemoon-gu, Seoul, 03760, Republic of Korea. park.yoonjung@ewha.ac.kr.
authors.forename: Yoon Jung
authors.identifier: http://orcid.org/0000-0001-6999-4996
authors.initials: YJ
authors.lastname: Park
mesh_terms: D000107:Acetylation; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D044127:Epigenesis, Genetic / Q000187:drug effects*; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D018696:Neuroprotective Agents / Q000737:chemistry / Q000494:pharmacology*; D029596:Paeonia / Q000737:chemistry*; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D006657:Histones; D018696:Neuroprotective Agents; D010936:Plant Extracts; D051547:Heme Oxygenase-1
keywords: Epigenetics; Histone acetylation; MPP+-induced cell death; Neuroprotective effect; Paeonia lactiflora