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

Park, SA; Park, HJ; Lee, BI; Ahn, YH; Kim, SU; Choi, KS
Brain research. Molecular brain research, 93(1):18-26, 2001
Journal Title
Brain research. Molecular brain research
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
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
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