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Correlation between structure of Bcl-2 and its inhibitory function of JNK and caspase activity in dopaminergic neuronal apoptosis

DC FieldValueLanguage
dc.contributor.author장인익-
dc.date.accessioned2019-11-11T05:14:41Z-
dc.date.available2019-11-11T05:14:41Z-
dc.date.issued2000-
dc.identifier.issn0022-3042-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/171725-
dc.description.abstractTo examine the correlation between the structure of Bcl-2 and its inhibitory function of c-Jun N-terminal kinase (JNK) and caspase activity, we established a dopaminergic neuronal cell line, MN9D overexpressing Bcl-2 (MN9D/Bcl-2) or its structural mutants. The mutants comprised a point mutation in the BH1 (G145A; MN9D/BH1) or BH2 (W188A; MN9D/BH2) domain and a deletion mutation in the C-terminal (MN9D/C22), BH3 (MN9D/BH3), or BH4 (MN9D/BH4) domain. As determined by the TUNEL (terminal deoxynucleotidyltransferase nick end-labeling) and MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] reduction assay, apoptotic death of MN9D/Neo cells reached 80-90% within 24 h in response to 1 microM staurosporine. Upon staurosporine treatment, JNK activity increased six- to sevenfold over the basal level within 2-4 h. Treatment of MN9D/Neo with both staurosporine and a caspase inhibitor, Z-VAD, attenuated cell death without suppressing JNK activation. Both staurosporine-induced cell death and JNK activation were attenuated in MN9D/Bcl-2. As determined by cleavage of poly(ADP-ribose) polymerase into 85 kDa, Bcl-2 blocked caspase activity as well. When cells overexpressing one of the Bcl-2 mutants were treated with staurosporine, death was attenuated in MN9D/BH1, MN9D/BH2, and MN9D/C22 but not in MN9D/BH3 and MN9D/BH4. Similarly, both JNK and caspase activation were blocked in MN9D/BH1, MN9D/BH2, and MN9D/C22, whereas they were not suppressed in MN9D/BH3 and MN9D/BH4. Taken together, our data indicate that there exists a close structural and functional correlation of Bcl-2 to JNK and caspase activity in staurosporine-induced dopaminergic neuronal cell death.-
dc.description.statementOfResponsibilityopen-
dc.languageEnglish-
dc.publisherWiley-
dc.relation.isPartOfJournal of Neurochemistry-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.subject.MESHApoptosis/drug effects-
dc.subject.MESHApoptosis/physiology*-
dc.subject.MESHCaspases/metabolism*-
dc.subject.MESHCells, Cultured-
dc.subject.MESHDopamine/physiology-
dc.subject.MESHEnzyme Inhibitors/pharmacology-
dc.subject.MESHHumans-
dc.subject.MESHIn Situ Nick-End Labeling-
dc.subject.MESHJNK Mitogen-Activated Protein Kinases-
dc.subject.MESHMitogen-Activated Protein Kinases/metabolism*-
dc.subject.MESHMutation/physiology-
dc.subject.MESHNeurons/cytology*-
dc.subject.MESHNeurons/enzymology*-
dc.subject.MESHParkinson Disease/metabolism-
dc.subject.MESHProtein Structure, Tertiary-
dc.subject.MESHProto-Oncogene Proteins c-bcl-2/chemistry-
dc.subject.MESHProto-Oncogene Proteins c-bcl-2/genetics-
dc.subject.MESHProto-Oncogene Proteins c-bcl-2/metabolism*-
dc.subject.MESHStaurosporine/pharmacology-
dc.subject.MESHStructure-Activity Relationship-
dc.subject.MESHTransfection-
dc.titleCorrelation between structure of Bcl-2 and its inhibitory function of JNK and caspase activity in dopaminergic neuronal apoptosis-
dc.typeArticle-
dc.contributor.collegeCollege of Dentistry (치과대학)-
dc.contributor.departmentDept. of Oral Biology (구강생물학교실)-
dc.contributor.googleauthorWon-Seok Choi-
dc.contributor.googleauthorSo-Young Yoon-
dc.contributor.googleauthorIn Ick Chang-
dc.contributor.googleauthorEui-Ju Choi-
dc.contributor.googleauthorHyewhon Rhim-
dc.contributor.googleauthorByung K. Jin-
dc.contributor.googleauthorTae H. Oh-
dc.contributor.googleauthorStanislaw Krajewski-
dc.contributor.googleauthorJohn C. Reed-
dc.contributor.googleauthorYoung J. Oh-
dc.identifier.doi10.1046/j.1471-4159.2000.0741621.x-
dc.contributor.localIdA03461-
dc.relation.journalcodeJ01620-
dc.identifier.eissn1471-4159-
dc.identifier.pmid10737620-
dc.subject.keywordApoptosis-
dc.subject.keywordBcl‐2 homology domain-
dc.subject.keywordMN9D-
dc.subject.keywordParkinson's disease-
dc.contributor.alternativeNameChang, In Ik-
dc.contributor.affiliatedAuthor장인익-
dc.citation.volume74-
dc.citation.number4-
dc.citation.startPage1621-
dc.citation.endPage1626-
dc.identifier.bibliographicCitationJournal of Neurochemistry, Vol.74(4) : 1621-1626, 2000-
Appears in Collections:
2. College of Dentistry (치과대학) > Dept. of Oral Biology (구강생물학교실) > 1. Journal Papers

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