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Cysteine cathepsins are not involved in Fas/CD95 signalling in primary<br />
skin fibroblasts<br />
Lea Bojič1, Ana Petelin1, Veronika Stoka1, Thomas Reinheckel2, Christoph Peters2, Vito<br />
Turk1, Boris Turk1<br />
1Dept. <strong>of</strong> Biochemistry, Molecular and Structural Biology, J. Stefan Institute, Jamova 39, SI-1000<br />
Ljubljana, Slovenia; 2Institut für Molekulare Medizin und Zellforschung, Albert-Ludwigs-Universität,<br />
Breisacherstr. 66, D-79106 Freiburg, Germany<br />
The potential role <strong>of</strong> cysteine cathepsins, especially cathepsin B, in Fas/CD95-induced<br />
apoptosis was investigated using wild-type and cathepsin B –deficient primary skin<br />
fibroblasts. Apoptosis was induced with an anti-Fas/CD95 antibody in the presence <strong>of</strong><br />
cycloheximide and no difference was observed between the two genotypes. Preincubation<br />
<strong>of</strong> cells with the broad spectrum cathepsin inhibitor E-64d had neither an effect on<br />
apoptosis progression. First signs <strong>of</strong> mitochondria damage were observed ~3 hours post<br />
apoptosis induction, whereas a significant number <strong>of</strong> cells with damaged mitochondria<br />
was seen after 11 hours. In contrast, lysosome damage was only seen after 15 hours with<br />
no difference between the two genotypes. In addition, Bid cleavage was found to be<br />
diminished in cathepsin B-deficient cells. These results suggest that cysteine cathepsins<br />
have no active role in Fas/CD95 apoptosis and that lysosomal damage and diminished Bid<br />
cleavage observed are probably late bystander events.<br />
p5<br />
87
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