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Cell Death Differ. 2003 Nov;10(11):1253-9.

Cathepsin D mediates cytochrome c release and caspase activation in human fibroblast apoptosis induced by staurosporine.

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1
Division of Pathology II, Faculty of Health Sciences, Linköping University, S-58185 Linköping, Sweden. lotta.johansson@inr.liu.se

Abstract

There is increasing evidence that proteases other than caspases, for example, the lysosomal cathepsins B, D and L, are involved in apoptotic cell death. In the present study, we present data that suggest a role for cathepsin D in staurosporine-induced apoptosis in human foreskin fibroblasts. Cathepsin D and cytochrome c were detected partially released to the cytosol after exposure to 0.1 muM staurosporine for 1 h. After 4 h, activation of caspase-9 and -3 was initiated and later caspase-8 activation and a decrease in full-length Bid were detected. Pretreatment of cells with the cathepsin D inhibitor, pepstatin A, prevented cytochrome c release and caspase activation, and delayed cell death. These results imply that cytosolic cathepsin D is a key mediator in staurosporine-induced apoptosis. Analysis of the relative sequence of apoptotic events indicates that, in this cell type, cathepsin D acts upstream of cytochrome c release and caspase activation.

PMID:
14576777
DOI:
10.1038/sj.cdd.4401290
[Indexed for MEDLINE]
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