Document Detail


Cell cycle events mediate lactacystin-induced apoptotic death of neuronal PC12 cells.
MedLine Citation:
PMID:  20658965     Owner:  NLM     Status:  In-Process    
Abstract/OtherAbstract:
Dysfunction of the UPS (ubiquitin-proteasome system) has been implicated in dopaminergic neuronal death in PD (Parkinson's disease). Recent studies suggest that unregulated cell cycle events play a key role in neuronal death. In this study, the effects of UPS dysfunction on cell cycle events in neuronal differentiated PC12 cells were analysed using a specific inhibitor of proteasome, lactacystin. Lactacystin induced apoptosis, G₂/M cell cycle arrest and sustained the phosphorylation of the pRB (retinoblastoma protein), the key molecular process of G₁/S transition, in neuronal PC12 cells. Furthermore, inhibition of cell cycle progression protected against lactacystin-induced cell apoptosis. Finally, we determined that lactacystin activated the ERK signalling pathway. Inhibition of ERK1/2 activation by MEK-1 inhibitor PD98059 decreased cell cycle aberrant and prevented apoptosis induced by lactacystin. These results indicate that aberrant cell cycle events contribute to apoptotic death induced by UPS dysfunction.
Authors:
Zhentao Zhang; Yan Xu; Kairong Qin; Tao Wang; Xuebing Cao
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cell biology international     Volume:  34     ISSN:  1095-8355     ISO Abbreviation:  Cell Biol. Int.     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-11-11     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9307129     Medline TA:  Cell Biol Int     Country:  England    
Other Details:
Languages:  eng     Pagination:  1181-7     Citation Subset:  IM    
Affiliation:
Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Peoples Republic of China.
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