Abstract
Apoptosis can be mediated by mechanisms other than the traditional caspase-mediated cleavage cascade. There is growing recognition that alternative proteolytic enzymes such as the lysosomal cathepsin proteases can initiate or propagate proapoptotic signals, but it is currently unclear how cathepsins achieve these actions. Recent in vitro evidence suggests that cathepsins cleave the proapoptotic Bcl-2 family member Bid, thereby activating it and allowing it to induce the mitochondrial release of cytochrome c and subsequent apoptosis. We have tested this hypothesis in vivo by breeding mice that lack cathepsin inhibition (cystatin B-deficient mice) to Bid-deficient mice, to determine whether the apoptosis caused by cathepsins is dependent on Bid signaling. We found that cathepsins are still able to promote apoptosis even in the absence of Bid, indicating that these proteases mediate apoptosis via a different pathway, or that some other molecule can functionally substitute for Bid in this system.
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Abbreviations
- EPM1:
-
Unverricht–Lundborg progressive myoclonus epilepsy
- TUNEL:
-
terminal deoxynucleotidyl transferase dUTP nick-end labeling
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Acknowledgements
We are grateful to Loan Nguyen for assistance with mouse genotyping. We thank Dr. Ravi Tolwani for use of the rotor rod apparatus. MKH was supported by an Epilepsy Foundation postdoctoral fellowship through the generous support of the American Epilepsy Society and the Milken Family Foundation. AV and JLN were supported by NINDS grant NS29709. X-MY was supported by grant CA 83817.
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Houseweart, M., Vilaythong, A., Yin, XM. et al. Apoptosis caused by cathepsins does not require Bid signaling in an in vivo model of progressive myoclonus epilepsy (EPM1). Cell Death Differ 10, 1329–1335 (2003). https://doi.org/10.1038/sj.cdd.4401309
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DOI: https://doi.org/10.1038/sj.cdd.4401309
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