Cathepsin D mediates cytochrome c release and caspase activation in human fibroblast apoptosis induced by staurosporine
2003 (English)In: Cell Death and Differentiation, ISSN 1350-9047 (print) 1476-5403 (online), Vol. 10, no 11, 1253-1259 p.Article in journal (Refereed) Published
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 µM 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.
Place, publisher, year, edition, pages
2003. Vol. 10, no 11, 1253-1259 p.
apoptosis, caspases, cathepsin D, cytochrome c, fibroblasts, lysosomes
National CategoryMedical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-13200DOI: 10.1038/sj.cdd.4401290OAI: oai:DiVA.org:liu-13200DiVA: diva2:18025