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Cell cycle events mediate lactacystin‐induced apoptotic death of neuronal PC12 cells
Author(s) -
Zhang Zhentao,
Xu Yan,
Qin Kairong,
Wang Tao,
Cao Xuebing
Publication year - 2010
Publication title -
cell biology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.932
H-Index - 77
eISSN - 1095-8355
pISSN - 1065-6995
DOI - 10.1042/cbi20090079
Subject(s) - lactacystin , proteasome , microbiology and biotechnology , cell cycle , apoptosis , programmed cell death , biology , proteasome inhibitor , cell cycle checkpoint , biochemistry
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, G 2 /M cell cycle arrest and sustained the phosphorylation of the pRB (retinoblastoma protein), the key molecular process of G 1 /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.