Decreased apoptotic response of inclusion-cell disease fibroblasts: A consequence of lysosomal enzyme missorting?
2002 (English)In: Experimental Cell Research, ISSN 0014-4827, Vol. 274, no 1Article in journal (Refereed) Published
To better understand the role of lysosomes in apoptosis, we compared the responses to apoptotic stimuli of normal fibroblasts with those of inclusion cells (I-cells), i.e., fibroblasts with impaired function of lysosomal enzymes due to their missorting and ensuing nonlysosomal localization. Although both cell types did undergo apoptosis when exposed to the lysosomotropic detergent MSDH, the redox-cycling quinone naphthazarin, or the protein kinase inhibitor staurosporine, I-cells exerted a markedly decreased response to these agonists than did normal fibroblasts. Furthermore, leupeptin and pepstatin A (inhibitors of cysteine and aspartic proteases, respectively) suppressed staurosporine-induced apoptosis of normal fibroblasts, whereas survival of I-cells was unaffected. These findings give further support for the involvement of lysosomal enzymes in apoptosis and suggest I-cells as a suitable model for studying the role of lysosomes in programmed cell death.
Place, publisher, year, edition, pages
2002. Vol. 274, no 1
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-27706DOI: 10.1006/excr.2001.5441Local ID: 12444OAI: oai:DiVA.org:liu-27706DiVA: diva2:248258