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

Johansson, Ann-CharlotteLinköpings universitet,Experimentell patologi,Hälsouniversitetet (författare)

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.

Steen, Håkan (författare)
Öllinger, KarinÖstergötlands Läns Landsting,Linköpings universitet,Experimentell patologi,Hälsouniversitetet,Klinisk patologi och klinisk genetik(Swepub:liu)karol56 (författare)
Roberg, KarinÖstergötlands Läns Landsting,Linköpings universitet,Oto-Rhino-Laryngologi,Hälsouniversitetet,Öronkliniken US(Swepub:liu)karro26 (författare)
Linköpings universitetExperimentell patologi (creator_code:org_t)

Ingår i:Cell Death and Differentiation: Springer Science and Business Media LLC10:11, s. 1253-12591350-90471476-5403

Av författaren/redakt...: Johansson, Ann-C ...; Steen, Håkan; Öllinger, Karin; Roberg, Karin

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