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Title: Calpain activation after mitochondrial permeability transition in microcystin-induced cell death in rat hepatocytes
Authors: Ding, W.-X.
Shen, H.-M. 
Ong, C.-N. 
Keywords: Apoptosis
Electron transport chain
Intracellular Ca2+
Oxidative stress
Issue Date: 2002
Citation: Ding, W.-X., Shen, H.-M., Ong, C.-N. (2002). Calpain activation after mitochondrial permeability transition in microcystin-induced cell death in rat hepatocytes. Biochemical and Biophysical Research Communications 291 (2) : 321-331. ScholarBank@NUS Repository.
Abstract: Previous studies have shown that microcystin-LR (MLR), a specific hepatotoxin, induces onset of mitochondrial permeability transition (MPT) and apoptosis in cultured rat hepatocytes. Here we attempted to investigate the downstream events after the onset of MPT in MLR-treated hepatocytes. Various mitochondrial electron transport chain (ETC) inhibitors effectively prevented the onset of MPT, suggesting that the mitochondrial ETC plays an important role in MLR-induced MPT. MLR also induced mitochondrial cytochrome c release, which can be prevented by a specific MPT inhibitor (cyclosporin A, CsA), and by various ETC inhibitors. Interestingly, the release of cytochrome c did not activate caspase-9 and -3, the main caspases involved in apoptosis. Instead, MLR activated calpain in rat hepatocytes, probably through the increase of intracellular Ca2+ released from mitochondria. Both ALLN and ALLM, two calpain inhibitors, significantly blocked MLR-induced calpain activation and subsequent cell death. CsA also prevented MLR-induced calpain activation and cell death, suggesting that the activation of calpain may be a post-mitochondrial event. These data demonstrate for the first time that calpain rather than caspases plays an important role in MLR-induced apoptosis. © 2002 Elsevier Science (USA).
Source Title: Biochemical and Biophysical Research Communications
ISSN: 0006291X
DOI: 10.1006/bbrc.2002.6453
Appears in Collections:Staff Publications

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