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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.
Ju, Da-Tong; Sivalingam, Kalaiselvi; Kuo, Wei-Wen; Ho, Tsung-Jung; Chang, Ruey-Lin; Chung, Li-Chin; Day, Cecilia Hsuan; Viswanadha, Vijaya Padma; Liao, Po-Hsiang; Huang, Chih-Yang.
Afiliación
  • Ju DT; Department of Neurological Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan.
  • Sivalingam K; Department of Medical Research, China Medical University Hospital, China Medical University, Taichung 404, Taiwan.
  • Kuo WW; Department of Biological Science and Technology, China Medical University, Taichung 404, Taiwan.
  • Ho TJ; Department of Chinese Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Tzu Chi University, Hualien 970, Taiwan.
  • Chang RL; School of Post-Baccalaureate Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung 404, Taiwan.
  • Chung LC; Department of Hospital and Health Care Administration, Chia Nan University of Pharmacy & Science, Tainan 717, Taiwan.
  • Day CH; Department of Nursing, MeiHo University, Pingtung 912, Taiwan.
  • Viswanadha VP; Department of Biotechnology, Bharathiar University, Tamilnadu 641046, India.
  • Liao PH; Cardiovascular and Mitochondria related diseases research center, Hualien Tzu Chi Hospital, Hualien 970, Taiwan.
  • Huang CY; Center of General Education, Buddhist Tzu Chi Medical Foundation, Tzu Chi University of Science and Technology, Hualien 970, Taiwan.
Nutrients ; 11(7)2019 Jul 19.
Article en En | MEDLINE | ID: mdl-31331066
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Paraquat / Enfermedad de Parkinson / Receptor IGF Tipo 1 / Apoptosis / Fosfatidilinositol 3-Quinasas / Alcaloides Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: Nutrients Año: 2019 Tipo del documento: Article País de afiliación: Taiwán Pais de publicación: Suiza
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Paraquat / Enfermedad de Parkinson / Receptor IGF Tipo 1 / Apoptosis / Fosfatidilinositol 3-Quinasas / Alcaloides Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: Nutrients Año: 2019 Tipo del documento: Article País de afiliación: Taiwán Pais de publicación: Suiza