9 240

Cited 0 times in

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

Authors
Park, SA; Park, HJ; Lee, BI; Ahn, YH; Kim, SU; Choi, KS
Citation
Brain research. Molecular brain research, 93(1):18-26, 2001
Journal Title
Brain research. Molecular brain research
ISSN
0169-328X
Abstract
Bcl-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.
MeSH terms
AnimalsAntineoplastic Agents/pharmacologyApoptosis/drug effectsApoptosis/physiology*Cisplatin/pharmacologyGene Expression/physiologyMitogen-Activated Protein Kinases/metabolism*Neuroblastoma*Proto-Oncogene Proteins/geneticsProto-Oncogene Proteins c-bcl-2/genetics*RatsTumor Cells, CulturedTumor Suppressor Protein p53/metabolism*bcl-2-Associated X Protein
PMID
11532334
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
AJOU Authors
김, 승업최, 경숙
Full Text Link
Export
RIS (EndNote)
XLS (Excel)
XML

qrcode

해당 아이템을 이메일로 공유하기 원하시면 인증을 거치시기 바랍니다.

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse