The lysosomal protease cathepsin D mediates apoptosis induced by oxidative stress

Abstract

SPECIFIC AIMSThe overall objective of the present study was to examine lysosomal stability during apoptosis and the relationship between caspase activation and the lysosomal proteases cathepsins D and B with regard to their effects on apoptosis.PRINCIPAL FINDINGS1. Naphthazarin-induced apoptosis is dependent on the lysosomal protease cathepsin DThe caspase-3-like activity increased after 12 h of treatment with the redox cycling quinone naphthazarine (NZ). By comparison, the activity of cathepsin D was augmented after 4 h of NZ treatment and peaked at 16 h (Fig. 1A⤻ , B⤻ ). Moreover, increased levels of p53, a transcription factor for cathepsin D, were detected after exposure to NZ for 4 h (Fig. 1D⤻ ). The total protein level did not change in response to p53 induction and was estimated to 8.2 ± 3.5, 8.0 ± 2.1, and 7.1 ± 1.4 μg protein/10 000 cells after 0, 12, and 20 h respectively. We also found that NZ caused a rapid decrease in the activity of the lysosomal cysteine protease cathepsin B (Fig. 1C⤻ ). Fi...