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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, NS
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.

History

Publication title

Neuroscience Letters: An International Multidisciplinary Journal Devoted to The Rapid Publication of Basic Research in Neurosciences

Volume

397

Issue

1-2

Pagination

69-73

ISSN

0304-3940

Department/School

Menzies Institute for Medical Research

Publisher

Elsevier Sci Ireland Ltd

Place of publication

Customer Relations Manager, Bay 15, Shannon Industrial Estate Co, Clare, Ireland

Repository Status

  • Restricted

Socio-economic Objectives

Clinical health not elsewhere classified

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