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Early induction of calpains in rotenone-mediated neuronal apoptosis
journal contribution
posted on 2023-05-17, 01:42 authored by Chen, MJ, Yap, YW, Choy, MS, Koh, CH, Seet, SJ, Duan, W, Whiteman, M, Cheung, NSRotenone 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.
History
Publication title
Neuroscience Letters: An International Multidisciplinary Journal Devoted to The Rapid Publication of Basic Research in NeurosciencesVolume
397Issue
1-2Pagination
69-73ISSN
0304-3940Department/School
Menzies Institute for Medical ResearchPublisher
Elsevier Sci Ireland LtdPlace of publication
Customer Relations Manager, Bay 15, Shannon Industrial Estate Co, Clare, IrelandRepository Status
- Restricted