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

doi:10.3390/nu11071655

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Title:	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
Authors:	Ju, Da-Tong Sivalingam, Kalaiselvi Kuo, Wei-Wen Ho, Tsung-Jung Chang, Ruey-Lin Li-Chin Chung(鍾麗琴) Day, Cecilia Hsuan Viswanadha, Vijaya Padma Liao, Po-Hsiang Huang, Chih-Yang
Contributors:	Natl Def Med Ctr, Triserv Gen Hosp, Dept Neurol Surg China Med Univ, China Med Univ Hosp, Dept Med Res China Med Univ, Dept Biol Sci & Technol, Taichung 404, Taiwan Tzu Chi Univ, Buddhist Tzu Chi Med Fdn, Hualien Tzu Chi Hosp, Dept Chinese Med China Med Univ, Coll Chinese Med, Sch Postbaccalaureate Chinese Med Chia Nan Univ Pharm & Sci, Dept Hosp & Hlth Care Adm MeiHo Univ, Dept Nursing Bharathiar Univ, Dept Biotechnol Hualien Tzu Chi Hosp, Cardiovasc & Mitochondria Related Dis Res Ctr Tzu Chi Univ Sci & Technol, Buddhist Tzu Chi Med Fdn, Ctr Gen Educ China Med Univ & Hosp, Grad Inst Biomed Asia Univ, Dept Biotechnol
Keywords:	parkinson's disease vasicinone paraquat apoptosis reactive oxygen species neuroprotection
Date:	2019-07
Issue Date:	2020-07-29 13:52:41 (UTC+8)
Publisher:	MDPI
Abstract:	Vasicinone is a quinazoline alkaloid isolated from the Adhatoda vasica 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.
Relation:	Nutrients, v.11, n.7, 1655
Appears in Collections:	[Dept. of Hospital and Health (including master's program)] Periodical Articles

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