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

Authors
 Sun Ah Park  ;  Hyun Jin Park  ;  Byung In Lee  ;  Yong Ho Ahn  ;  Seung U Kim  ;  Kyeong Sook Choi 
Citation
 MOLECULAR BRAIN RESEARCH , Vol.93(1) : 18-26, 2001 
Journal Title
 MOLECULAR BRAIN RESEARCH 
ISSN
 0169-328X 
Issue Date
2001
MeSH
Animals ; Antineoplastic Agents/pharmacology ; Apoptosis/drug effects ; Apoptosis/physiology* ; Cisplatin/pharmacology ; Gene Expression/physiology ; Mitogen-Activated Protein Kinases/metabolism* ; Neuroblastoma* ; Proto-Oncogene Proteins/genetics ; Proto-Oncogene Proteins c-bcl-2/genetics* ; Rats ; Tumor Cells, Cultured ; Tumor Suppressor Protein p53/metabolism* ; bcl-2-Associated X Protein
Keywords
Apoptosis ; Bcl-2 ; Cisplatin ; Extracellular signal-regulated kinase ; p53 ; B104 cell
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.
Full Text
http://www.sciencedirect.com/science/article/pii/S0169328X01001760?np=y
DOI
10.1016/S0169-328X(01)00176-0
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Neurology (신경과학교실) > 1. Journal Papers
Yonsei Authors
Ahn, Yong Ho(안용호) ORCID logo https://orcid.org/0000-0002-4133-0757
Lee, Byung In(이병인)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/142185
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