Sensitization of stefin B-deficient thymocytes towards staurosporin-induced apoptosis is independent of cysteine cathepsins

Abstract
Stefin B (cystatin B) is an inhibitor of lysosomal cysteine cathepsins and does not inhibit cathepsin D, E (aspartic) or cathepsin G (serine) proteinases. In this study, we have investigated apoptosis triggered by camptothecin, staurosporin (STS), and anti‐CD95 monoclonal antibody in the thymocytes from the stefin B‐deficient mice and wild‐type mice. We have observed increased sensibility to STS‐induced apoptosis in the thymocytes of stefin B‐deficient mice. Pretreatment of cells with pan‐caspase inhibitor z‐Val‐Ala‐Asp(OMe)‐fluoromethylketone completely inhibited phosphatidylserine externalization and caspase activation, while treatment with inhibitor of calpains‐ and papain‐like cathepsins (2S,3S)‐trans‐epoxysuccinyl‐leucylamido‐3‐methyl‐butane ethyl ester did not prevent caspase activation nor phosphatidylserine exposure. We conclude that sensitization to apoptosis induced by STS in thymocytes of stefin B‐deficient and wild‐type mice is not dependent on cathepsin inhibition by stefin B.