Cited 25 times in
Correlation between structure of Bcl-2 and its inhibitory function of JNK and caspase activity in dopaminergic neuronal apoptosis
DC Field | Value | Language |
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dc.contributor.author | 장인익 | - |
dc.date.accessioned | 2019-11-11T05:14:41Z | - |
dc.date.available | 2019-11-11T05:14:41Z | - |
dc.date.issued | 2000 | - |
dc.identifier.issn | 0022-3042 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/171725 | - |
dc.description.abstract | To 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.statementOfResponsibility | open | - |
dc.language | English | - |
dc.publisher | Wiley | - |
dc.relation.isPartOf | Journal of Neurochemistry | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.subject.MESH | Apoptosis/drug effects | - |
dc.subject.MESH | Apoptosis/physiology* | - |
dc.subject.MESH | Caspases/metabolism* | - |
dc.subject.MESH | Cells, Cultured | - |
dc.subject.MESH | Dopamine/physiology | - |
dc.subject.MESH | Enzyme Inhibitors/pharmacology | - |
dc.subject.MESH | Humans | - |
dc.subject.MESH | In Situ Nick-End Labeling | - |
dc.subject.MESH | JNK Mitogen-Activated Protein Kinases | - |
dc.subject.MESH | Mitogen-Activated Protein Kinases/metabolism* | - |
dc.subject.MESH | Mutation/physiology | - |
dc.subject.MESH | Neurons/cytology* | - |
dc.subject.MESH | Neurons/enzymology* | - |
dc.subject.MESH | Parkinson Disease/metabolism | - |
dc.subject.MESH | Protein Structure, Tertiary | - |
dc.subject.MESH | Proto-Oncogene Proteins c-bcl-2/chemistry | - |
dc.subject.MESH | Proto-Oncogene Proteins c-bcl-2/genetics | - |
dc.subject.MESH | Proto-Oncogene Proteins c-bcl-2/metabolism* | - |
dc.subject.MESH | Staurosporine/pharmacology | - |
dc.subject.MESH | Structure-Activity Relationship | - |
dc.subject.MESH | Transfection | - |
dc.title | Correlation between structure of Bcl-2 and its inhibitory function of JNK and caspase activity in dopaminergic neuronal apoptosis | - |
dc.type | Article | - |
dc.contributor.college | College of Dentistry (치과대학) | - |
dc.contributor.department | Dept. of Oral Biology (구강생물학교실) | - |
dc.contributor.googleauthor | Won-Seok Choi | - |
dc.contributor.googleauthor | So-Young Yoon | - |
dc.contributor.googleauthor | In Ick Chang | - |
dc.contributor.googleauthor | Eui-Ju Choi | - |
dc.contributor.googleauthor | Hyewhon Rhim | - |
dc.contributor.googleauthor | Byung K. Jin | - |
dc.contributor.googleauthor | Tae H. Oh | - |
dc.contributor.googleauthor | Stanislaw Krajewski | - |
dc.contributor.googleauthor | John C. Reed | - |
dc.contributor.googleauthor | Young J. Oh | - |
dc.identifier.doi | 10.1046/j.1471-4159.2000.0741621.x | - |
dc.contributor.localId | A03461 | - |
dc.relation.journalcode | J01620 | - |
dc.identifier.eissn | 1471-4159 | - |
dc.identifier.pmid | 10737620 | - |
dc.subject.keyword | Apoptosis | - |
dc.subject.keyword | Bcl‐2 homology domain | - |
dc.subject.keyword | MN9D | - |
dc.subject.keyword | Parkinson's disease | - |
dc.contributor.alternativeName | Chang, In Ik | - |
dc.contributor.affiliatedAuthor | 장인익 | - |
dc.citation.volume | 74 | - |
dc.citation.number | 4 | - |
dc.citation.startPage | 1621 | - |
dc.citation.endPage | 1626 | - |
dc.identifier.bibliographicCitation | Journal of Neurochemistry, Vol.74(4) : 1621-1626, 2000 | - |
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