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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.
Eur J Pharmacol. 2011 Jan 10; 650(1):48-57.EJ

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.

Authors+Show Affiliations

Department of Biotechnology, Konkuk University, Chungju, 380-701, South Korea.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20946892

Citation

Kim, In Su, et al. "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." European Journal of Pharmacology, vol. 650, no. 1, 2011, pp. 48-57.
Kim IS, Koppula S, Kim BW, et al. 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. Eur J Pharmacol. 2011;650(1):48-57.
Kim, I. S., Koppula, S., Kim, B. W., Song, M. D., Jung, J. Y., Lee, G., Lee, H. S., & Choi, D. K. (2011). 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. European Journal of Pharmacology, 650(1), 48-57. https://doi.org/10.1016/j.ejphar.2010.09.063
Kim IS, et al. 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. Eur J Pharmacol. 2011 Jan 10;650(1):48-57. PubMed PMID: 20946892.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Kim,In Su, AU - Koppula,Sushruta, AU - Kim,Byung Wook, AU - Song,Min Dong, AU - Jung,Ju Yeon, AU - Lee,Gwang, AU - Lee,Hee Soon, AU - Choi,Dong-Kug, Y1 - 2010/10/12/ PY - 2010/03/15/received PY - 2010/09/17/revised PY - 2010/09/20/accepted PY - 2010/10/16/entrez PY - 2010/10/16/pubmed PY - 2011/3/25/medline SP - 48 EP - 57 JF - European journal of pharmacology JO - Eur J Pharmacol VL - 650 IS - 1 N2 - 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. SN - 1879-0712 UR - https://www.unboundmedicine.com/medline/citation/20946892/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_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(10)00984-2 DB - PRIME DP - Unbound Medicine ER -