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A novel synthetic compound PHID (8-Phenyl-6a, 7, 8, 9, 9a, 10-hexahydro-6H-isoindolo [5, 6-g] quinoxaline-7, 9-dione) protects SH-SY5Y cells against MPP(+)-induced cytotoxicity through inhibition of reactive oxygen species generation and JNK signaling.

Authors
Kim, IS; Koppula, S; Kim, BW; Song, MD; Jung, JY; Lee, G; Lee, HS; Choi, DK
Citation
European journal of pharmacology, 650(1):48-57, 2011
Journal Title
European journal of pharmacology
ISSN
0014-29991879-0712
Abstract
1-Methyl-4-phenylpyridinium ion (MPP(+)), a neurotoxin selective to dopaminergic neurons and an inhibitor of mitochondrial complex I, has been widely used as an etiologic model of Parkinson's disease. In this study, we investigated the protective effects of a novel synthetic compound, 8-Phenyl-6a,7,8,9,9a,10-hexahydro-6H-isoindolo[5,6-g]quinoxaline-7,9-dione (PHID), on MPP(+)-induced cytotoxicity in SH-SY5Y cells. MPP(+) induced apoptosis characterized by generation of reactive oxygen species, caspase-3 activation, poly ADP ribose polymerase proteolysis and increase in Bax/Bcl-2 ratio were blocked by PHID in a dose-dependent fashion. Furthermore, MPP(+)-mediated activation of stress-activated protein kinase/c-Jun N-terminal kinase (JNK) was also inhibited by PHID in a dose-dependent manner. The results indicate that PHID protects against MPP(+)-induced apoptosis by blocking reactive oxygen species stimulation and JNK signaling pathways in SH-SY5Y cells, implicating the novel compound in the prevention of progressive neurodegenerative diseases such as Parkinson's disease.
MeSH terms
1-Methyl-4-phenylpyridinium/*toxicityCaspase 3/metabolismCell Line, TumorCell Survival/drug effectsEnzyme Activation/drug effectsGene Expression Regulation/drug effectsHumansIsoindoles/chemical synthesis/*pharmacologyJNK Mitogen-Activated Protein Kinases/*metabolismMAP Kinase Signaling System/*drug effectsPoly(ADP-ribose) Polymerases/metabolismProto-Oncogene Proteins c-bcl-2/geneticsQuinoxalines/chemical synthesis/*pharmacologyReactive Oxygen Species/*metabolismbcl-2-Associated X Protein/geneticsp38 Mitogen-Activated Protein Kinases/metabolism
DOI
10.1016/j.ejphar.2010.09.063
PMID
20946892
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Journal Papers > School of Medicine / Graduate School of Medicine > Physiology
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