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

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. Catheps...

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Published inCell death and differentiation Vol. 10; no. 11; pp. 1253 - 1259
Main Authors Johansson, A-C, Steen, H, Ollinger, K, Roberg, K
Format Journal Article
LanguageEnglish
Published England Nature Publishing Group 01.11.2003
Subjects
Apoptosis
Apoptosis - physiology
BH3 Interacting Domain Death Agonist Protein
Carrier Proteins - metabolism
Caspase 3
Caspase 8
Caspase 9
caspases
Caspases - metabolism
cathepsin D
Cathepsin D - antagonists & inhibitors
Cathepsin D - metabolism
Cell death
Cell Line
Cytochrome
cytochrome c
Cytochromes c - metabolism
Enzyme Inhibitors - pharmacology
Fibroblasts
Fibroblasts - drug effects
Fibroblasts - enzymology
Fibroblasts - ultrastructure
Health sciences
Humans
Kinases
lysosomes
Male
MEDICIN
MEDICINE
Microscopy
Microscopy, Electron
Mitochondria
Morphology
Pepstatins - pharmacology
Staurosporine - pharmacology
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Summary: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.
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ISSN:1350-9047
1476-5403
1476-5403
DOI:10.1038/sj.cdd.4401290