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On the role of major vault protein in the resistance of senescent human diploid fibroblasts to apoptosis

Cited 41 time in Web of Science Cited 43 time in Scopus
Authors
Ryu, S J; An, H J; Oh, Y S; Choi, H R; Ha, M K; Park, S C
Issue Date
2008-07-05
Publisher
Nature Publishing Group
Citation
Cell Death Differ 2008; 15(11): 1673-1680
Keywords
*Apoptosis/drug effects*Cell Aging/drug effectsChild, Preschool*DiploidyDown-Regulation/drug effectsFibroblasts/*cytology/drug effects/enzymologyHumansHydrogen Peroxide/pharmacologyJNK Mitogen-Activated Protein Kinases/metabolismMaleOrgan Specificity/drug effectsProto-Oncogene Proteins c-bcl-2/metabolismStaurosporine/pharmacologyStress, Physiological/drug effectsThapsigargin/pharmacologyVault Ribonucleoprotein Particles/*metabolism
Abstract
Major vault protein (MVP), the main component of vault complex, is overexpressed in many multidrug-resistant cancer cell lines, suggesting a possible role for MVP in cell signaling and survival. In this study, we have found that MVP is markedly increased in senescent human diploid fibroblasts (HDFs) as well as in aged organs. We examined whether MVP expression might be affected by apoptotic stress in an aging-dependent manner. We treated young and senescent HDFs with apoptosis-inducing agents such as H(2)O(2), staurosporine and thapsigargin, and monitored MVP expression. We found that MVP expression is markedly reduced in young HDFs but not in senescent HDFs, in response to apoptotic stresses. Downregulation of MVP increased the sensitivity of senescent HDFs to apoptosis. Also, the level of antiapoptotic B-cell lymphoma protein-2 (Bcl-2) was significantly reduced and the accumulation of c-Jun increased in MVP knocked-down senescent HDFs. Moreover, treatment of MVP knocked-down senescent HDFs with SP600125, a specific c-Jun NH(2)-terminal kinase (JNK) inhibitor, restored the level of Bcl-2 protein. Taken together, these results suggest that MVP is important in the resistance of senescent HDFs to apoptosis by modulation of Bcl-2 expression by JNK pathway.
ISSN
1350-9047 (Print)
Language
English
URI
http://www.nature.com/cdd/journal/v15/n11/pdf/cdd200896a.pdf

http://hdl.handle.net/10371/67507
DOI
https://doi.org/10.1038/cdd.2008.96
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College of Medicine/School of Medicine (의과대학/대학원)Dept. of Biochemistry & Molecular Biology (생화학교실)Journal Papers (저널논문_생화학교실)
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