Cited by 21Parkinson's Disease Mechanisms and TreatmentsCell death mechanisms and regulationNuclear Receptors and Signaling

β-Ecdysterone Protects SH-SY5Y Cells Against 6-Hydroxydopamine-Induced Apoptosis via Mitochondria-Dependent Mechanism: Involvement of p38MAPK–p53 Signaling Pathway

Pan, Zhi, Niu, Yingcai, Liang, Yini, Zhang, Xiaojie, Dong, Miaoxian·2016·Neurotoxicity Research

Abstract

Parkinson's disease (PD) is a neurological disorder pathologically characterized by loss of dopaminergic neurons in the substantia nigra. No curative therapy is available for PD. We recently found that phytoestrogen β-ecdysterone (β-Ecd) is able to reduce MPP(+)-induced apoptosis in PC12 cells. This study investigated the potential of β-Ecd to protect against SH-SY5Y cell apoptosis induced by the PD-related neurotoxin 6-hydroxydopamine (6-OHDA) and the underlying mechanism for this cytoprotection. In the present study, pretreatment with β-Ecd significantly reduced 6-OHDA-induced apoptosis of SH-SY5Y cells by a mitochondria-dependent pathway, as indicated by downregulation of Bax and PUMA (p53 upregulated modulator of apoptosis) expression, suppressing ΔΨm loss, inhibiting cytochrome c release, and attenuating caspase-9 activation. Furthermore, we showed that the inhibition of p38 mitogen-activated protein kinase (p38(MAPK))-dependent p53 promoter activity contributed to the protection of SH-SY5Y cells from apoptosis, which was validated by the use of SB203580 or p38β dominant negative (DN) mutants. Additionally, knock-down apoptosis signal-regulating kinase 1 (ASK1) by specific shRNA and blockade reactive oxygen species (ROS) by pharmacological inhibitor competently prevented β-Ecd-mediated inhibition of p38(MAPK) and ASK1 phosphorylation, respectively. These data provide the first evidence that β-Ecd protects SH-SY5Y cells against 6-OHDA-induced apoptosis, possibly through mitochondria protection and p53 modulation via ROS-dependent ASK1-p38(MAPK) pathways. The neuroprotective effects of β-Ecd make it a promising candidate as a therapeutic agent for PD.

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Crossref · 10.1007/s12640-016-9631-7

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Authors
Pan, Z., Niu, Y., Liang, Y., Zhang, X., & Dong, M.
Affiliations
  • Changchun University of Chinese Medicine (CN)
  • Qiqihar Medical University (CN)
Corresponding author
Dong, Miaoxian
Venue
Neurotoxicity Research
Published
2016-05-26
Volume
30
Issue
3
Pages
453-466
ISSN
  • 1029-8428 (ISSN-L)
  • 1476-3524
OpenAlex
W2405993884
Cited by
21
References
48
Citations by year
2026: 3 · 2025: 2 · 2022: 2 · 2020: 2 · 2019: 4 · 2018: 5 · 2017: 3
FWCI
3.01
Type
journal article
Language
en
Open access
closed
Locations
  • Neurotoxicity Research (publishedVersion)
  • PubMed (publishedVersion)
Funders
The National Natural Science Foundation of China (81373629)
Topics
  • Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
Keywords
Parkinson's disease, 6-hydroxydopamine, neurotoxicity, apoptosis, SH-SY5Y cells, mitochondrial apoptosis, p38 MAPK, p53, ASK1, reactive oxygen species, cytochrome c release, caspase-9, Bax, PUMA, neuroprotection, phytoestrogens
MeSH terms
Antiparkinson Agents, Cell Survival, Drug Evaluation, Preclinical, Ecdysterone, Humans, Mitochondria, Proto-Oncogene Proteins, Tumor Suppressor Protein p53, Oxidopamine, Apoptosis, Reactive Oxygen Species, MAP Kinase Signaling System, Cytochromes c, Cell Line, Tumor, p38 Mitogen-Activated Protein Kinases, MAP Kinase Kinase Kinase 5, Apoptosis Regulatory Proteins, bcl-2-Associated X Protein, Caspase 9

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