Curcumin Protects an SH-SY5Y Cell Model of Parkinson’s Disease Against Toxic Injury by Regulating HSP90

Background/Aims: We aimed to explore the protective role of curcumin (Cur) in a cell model of Parkinson’s disease (PD) and its underlying mechanism. Methods: In this study, genes concerned with PD-related keywords were screened within DiGSeE database. The association network between Cur and selected...

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Veröffentlicht in:Cellular physiology and biochemistry Jg. 51; H. 2; S. 681 - 691
Hauptverfasser: Sang, Qiuling, Liu, Xiaoyang, Wang, Libo, Qi, Ling, Sun, Wenping, Wang, Weiyao, Sun, Yajuan , Zhang, Haina
Format: Journal Article
Sprache:Englisch
Veröffentlicht: Basel, Switzerland S. Karger AG 01.01.2018
Cell Physiol Biochem Press GmbH & Co KG
Schlagworte:
1-Methyl-4-phenylpyridinium - toxicity
Apoptosis
Apoptosis - drug effects
bcl-2-Associated X Protein - metabolism
bcl-X Protein - metabolism
Cell Line, Tumor
Cell Proliferation - drug effects
Curcumin
Curcumin - pharmacology
Dopamine - analysis
Dopamine Plasma Membrane Transport Proteins - metabolism
Dopaminergic neurons
Gene Regulatory Networks
Heat shock proteins
HSP90
HSP90 Heat-Shock Proteins - antagonists & inhibitors
HSP90 Heat-Shock Proteins - genetics
HSP90 Heat-Shock Proteins - metabolism
Humans
Kinases
Models, Biological
Morphology
MPP
Neurodegeneration
Original Paper
Parkinson
Parkinson Disease - metabolism
Parkinson Disease - pathology
Parkinson's disease
RNA Interference
RNA, Small Interfering - metabolism
SH-SY5Y
China
Dopaminergic neurons
HSP90
SH-SY5Y
Curcumin
MPP
Parkinson
ISSN:1015-8987, 1421-9778, 1421-9778
Online-Zugang:Volltext
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Zusammenfassung:Background/Aims: We aimed to explore the protective role of curcumin (Cur) in a cell model of Parkinson’s disease (PD) and its underlying mechanism. Methods: In this study, genes concerned with PD-related keywords were screened within DiGSeE database. The association network between Cur and selected genes was downloaded from STITCH, with the interactions analyzed by STRING. We built a mitochondrial toxin 1-methyl-4-phenylpyridinium (MPP + )-induced SH-SY5Y cell model of PD. Cell morphology was observed under an electron microscope. MTT assay was applied to detect cell proliferation rate. Western blot assay was conducted to determine the level of apoptotic markers, including cleaved caspase 3, Bcl-2-associated X protein (Bax) and B-cell lymphoma-extra-large (Bcl-xl). Tyrosine hydroxylase (TH), dopamine transporter (DAT) protein levels and dopamine (DA) concentration were identified as dopaminergic neuron markers and measured by western blotting or Enzyme-linked immunosorbent assay (ELISA). Results: Cur rescued the toxicity effects of MPP + on SH-SY5Y cells, by controlling morphological change, promoting cell proliferation and inhibiting apoptosis. Of all PD-related genes, HSP90 played an important role in Cur-gene network. HSP90 protein level was elevated by MPP + , whereas Cur could reverse this effect. Silencing of HSP90 significantly attenuated the curative effect introduced by Cur, while HSP90 overexpression enhanced the impact of Cur on PD. Conclusion: Cur can effectively inhibit the toxic effect of MPP + on SH-SY5Y cells and significantly reduce the adverse effects of MPP + on dopaminergic neurons via up-regulation of HSP90.
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ISSN:1015-8987
1421-9778
1421-9778
DOI:10.1159/000495326