Inhibition of cathepsin D prevents free-radical-induced apoptosis in rat cardiomyocytes
2000 (English)In: Archives of Biochemistry and Biophysics, ISSN 0003-9861, Vol. 373, no 2, 346-351 p.Article in journal (Refereed) Published
Apoptosis was inhibited in rat cardiomyocytes pretreated with the aspartic protease inhibitor pepstatin A and subsequently exposed to naphthazarin (5,8-dihydroxy-1,4-naphthoquinone). Cathepsin D was released from lysosomes to the cytosol upon exposure to naphthazarin, and the enzyme activity decreased simultaneously. Later, cathepsin D reappeared in granules of increased size, and enzyme activity was restored. Activation of caspase-3- like proteases was detected, and the number of cells showing apoptotic morphology increased with time. Pepstatin A pretreatment did not prevent release of cathepsin D from lysosomes but did significantly inhibit subsequent naphthazarin-induced caspase activation and apoptotic morphology. This suggests that cathepsin D exerts its apoptosis-stimulating effect upstream of caspase-3-like activation. (C) 2000 Academic Press.
Place, publisher, year, edition, pages
2000. Vol. 373, no 2, 346-351 p.
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-27973DOI: 10.1006/abbi.1999.1567Local ID: 12733OAI: oai:DiVA.org:liu-27973DiVA: diva2:248524