Nutrients, 2019-07, Vol.11 (7), p.1655
2019
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- Autor(en) / Beteiligte
- Titel
- Effect of Vasicinone against Paraquat-Induced MAPK/p53-Mediated Apoptosis via the IGF-1R/PI3K/AKT Pathway in a Parkinson's Disease-Associated SH-SY5Y Cell Model
- Ist Teil von
- Nutrients, 2019-07, Vol.11 (7), p.1655
- Ort / Verlag
- Switzerland: MDPI AG
- Erscheinungsjahr
- 2019
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Vasicinone is a quinazoline alkaloid isolated from the plant. In this study, we explored the neuroprotective effect and underlying molecular mechanism of vasicinone against paraquat-induced cellular apoptosis in SH-SY5Y cells. Vasicinone reduced the paraquat-induced loss of cell viability, rescued terminal deoxynucleotide transferase-mediated dUTP nick end-labeling (TUNEL)-positive apoptotic nuclei, and suppressed generation of reactive oxygen species (ROS) in a dose-dependent manner. Western blotting analysis revealed that vasicinone increased the phosphorylation of IGF1R/PI3K/AKT cell survival signaling molecules and downregulated the paraquat-induced, mitogen-activated protein kinase (MAPK)/c-Jun N-terminal kinase (JNK)-mediated apoptotic pathways compared to that observed in cells not treated with vasicinone. This protection depended critically on the activation of IGF1R, and the silencing of IGF1R by siRNA completely abrogated the protective effect of vasicinone in SH-SY5Y cells. Our findings indicated that vasicinone is a potential candidate for the treatment of Parkinson's disease and possibly other oxidative stress-related neurodegenerative disorders.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 2072-6643eISSN: 2072-6643DOI: 10.3390/nu11071655Titel-ID: cdi_doaj_primary_oai_doaj_org_article_84590bb091be415b84cbd8ab1c2c01eb
- Format
- –
- Schlagworte
- Alkaloids - pharmacology, Apoptosis, Apoptosis - drug effects, Cell Line, Cell Survival - drug effects, Humans, In Situ Nick-End Labeling, MAP Kinase Signaling System - drug effects, Medical research, neuroprotection, Neuroprotective Agents - pharmacology, paraquat, Paraquat - pharmacology, Parkinson Disease - drug therapy, Parkinson Disease - metabolism, Parkinson Disease - pathology, Parkinson's disease, Phosphatidylinositol 3-Kinases - metabolism, Phosphorylation - drug effects, Proto-Oncogene Proteins c-akt - metabolism, reactive oxygen species, Reactive Oxygen Species - antagonists & inhibitors, Receptor, IGF Type 1 - genetics, Receptor, IGF Type 1 - metabolism, Signal Transduction - drug effects, Tumor Suppressor Protein p53 - drug effects, Tumor Suppressor Protein p53 - metabolism, vasicinone