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Early induction of calpains in rotenone-mediated neuronal apoptosis

Citation

Chen, MJ and Yap, YW and Choy, MS and Koh, CH and Seet, SJ and Duan, W and Whiteman, M and Cheung, NS, Early induction of calpains in rotenone-mediated neuronal apoptosis, Neuroscience Letters: An International Multidisciplinary Journal Devoted to The Rapid Publication of Basic Research in Neurosciences, 397, (1-2) pp. 69-73. ISSN 0304-3940 (2006) [Refereed Article]

DOI: doi:10.1016/j.neulet.2005.12.011

Abstract

Rotenone is an inhibitor of mitochondrial complex I that produces a model of Parkinson's disease (PD), where neurons undergo apoptosis by caspase-dependent and/or caspase-independent pathways. Inhibition of calpains has recently been shown to attenuate neuronal apoptosis. This study aims to establish for the first time, the time-point of calpain activation with respect to the caspase activation and the possibility of cell cycle re-entry in rotenone-mediated cell death. Immunoblot results revealed calpain activation occurred at 5, 10 h prior to caspase-3 activation (at 15 h), suggesting calpain activation was an earlier cellular event compared to caspase activation in the rotenone-mediated apoptosis. In addition, an upregulation of phospho-p53 was observed at 21 h. However, no expression or upregulation of cell cycle regulatory proteins including cdc25a, cyclin-D1 and cyclin-D3 were observed, strongly suggesting that cell cycle re-entry did not occur. These findings provide new insights into the differential patterns of calpain and caspase activation that result from rotenone poisoning and which may be relevant to the therapeutic management of PD.

Item Details

Item Type:Refereed Article
Research Division:Medical and Health Sciences
Research Group:Neurosciences
Research Field:Cellular Nervous System
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Nervous System and Disorders
Author:Cheung, NS (Dr Nam Cheung)
ID Code:61607
Year Published:2006
Web of Science® Times Cited:29
Deposited By:Menzies Institute for Medical Research
Deposited On:2010-03-04
Last Modified:2010-05-03
Downloads:0

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