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Bcl-2 blocks cisplatin-induced apoptosis by suppression of ERK-mediated p53 accumulation in B104 cells.

DC Field Value Language
dc.contributor.authorPark, SA-
dc.contributor.authorPark, HJ-
dc.contributor.authorLee, BI-
dc.contributor.authorAhn, YH-
dc.contributor.authorKim, SU-
dc.contributor.authorChoi, KS-
dc.date.accessioned2011-08-25T04:51:57Z-
dc.date.available2011-08-25T04:51:57Z-
dc.date.issued2001-
dc.identifier.issn0169-328X-
dc.identifier.urihttp://repository.ajou.ac.kr/handle/201003/3935-
dc.description.abstractBcl-2 has been reported to inhibit neurotoxicity induced by cisplatin. However, neither the mechanism of cisplatin-induced neurotoxicity nor the mechanism by which Bcl-2 confers neuroprotection is clear. In this study, the signaling pathways involved in cisplatin-induced neurotoxicity were examined using a rat neuroblastoma cell line, B104. Treatment of B104 cells with cisplatin induced apoptosis, accompanying the accumulation of p53 and Bax protein. Interestingly, extracellular signal-regulated kinase 1/2 (ERK1/2) activities of MAP kinases were markedly enhanced prior to cisplatin-induced accumulation of p53 and Bax. Inhibition of ERK1/2 activities using PD98059, a selective MEK inhibitor, blocked the apoptotic cell death preventing cisplatin-induced accumulation of p53 and Bax. These results suggest that ERK mediates cisplatin-induced p53 activation to trigger apoptosis in B104 cells. Overexpression of Bcl-2 in B104 cells resulted in the complete resistance to cisplatin-induced apoptosis blocking ERK activation and the subsequent signaling pathway of p53. Our study clearly demonstrates that the action site of Bcl-2 localizes upstream of ERK in cisplatin-induced apoptotic signaling pathway.-
dc.language.isoen-
dc.subject.MESHAnimals-
dc.subject.MESHAntineoplastic Agents-
dc.subject.MESHApoptosis-
dc.subject.MESHCisplatin-
dc.subject.MESHGene Expression-
dc.subject.MESHMitogen-Activated Protein Kinases-
dc.subject.MESHNeuroblastoma-
dc.subject.MESHProto-Oncogene Proteins-
dc.subject.MESHProto-Oncogene Proteins c-bcl-2-
dc.subject.MESHRats-
dc.subject.MESHTumor Cells, Cultured-
dc.subject.MESHTumor Suppressor Protein p53-
dc.subject.MESHbcl-2-Associated X Protein-
dc.titleBcl-2 blocks cisplatin-induced apoptosis by suppression of ERK-mediated p53 accumulation in B104 cells.-
dc.typeArticle-
dc.identifier.pmid11532334-
dc.identifier.urlhttp://linkinghub.elsevier.com/retrieve/pii/S0169328X01001760-
dc.contributor.affiliatedAuthor김, 승업-
dc.contributor.affiliatedAuthor최, 경숙-
dc.type.localJournal Papers-
dc.citation.titleBrain research. Molecular brain research-
dc.citation.volume93-
dc.citation.number1-
dc.citation.date2001-
dc.citation.startPage18-
dc.citation.endPage26-
dc.identifier.bibliographicCitationBrain research. Molecular brain research, 93(1). : 18-26, 2001-
dc.relation.journalidJ00169328X-
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Neurology
Journal Papers > School of Medicine / Graduate School of Medicine > Biochemistry & Molecular Biology
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