Cysteine cathepsins are not involved in Fas/CD95 signalling in primary skin fibroblasts.
The potential role of cysteine cathepsins, especially cathepsin B, in Fas/CD95-induced apoptosis was investigated using wild-type and cathepsin B-deficient primary skin fibroblasts. Apoptosis was induced with an anti-Fas/CD95 antibody in the presence of cycloheximide and no difference was observed between the two genotypes. First cells with damaged mitochondria were observed approximately 3h post apoptosis induction and their number was significantly increased after 11h. In contrast, cells with damaged lysosomes were only seen after 15h with no difference between the two genotypes. Moreover, Bid cleavage was found to be diminished in cathepsin B-deficient cells. These results suggest that cysteine cathepsins have no active role in Fas/CD95 apoptosis.
Bojic
Lea
L
Department of Biochemistry, Molecular and Structural Biology, J. Stefan Institute, Jamova 39, SI-1000 Ljubljana, Slovenia.
Petelin
Ana
A
Stoka
Veronika
V
Reinheckel
Thomas
T
Peters
Christoph
C
Turk
Vito
V
Turk
Boris
B
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D051023:BH3 Interacting Domain Death Agonist Protein / Q000378:metabolism; D002401:Cathepsin B / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D008247:Lysosomes / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000378:metabolism; D015398:Signal Transduction; D012867:Skin / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013379:Substrate Specificity; D019014:fas Receptor / Q000378:metabolism*
D051023:BH3 Interacting Domain Death Agonist Protein; C494815:Bid protein, mouse; C491899:Fas protein, mouse; D019014:fas Receptor; D003513:Cycloheximide; D002401:Cathepsin B