Cysteine cathepsins are not critical for TRAIL- and CD95-induced apoptosis in several human cancer cell lines.

The potential role of cysteine cathepsins in tumor necrosis factor-related apoptosis-inducing ligand(TRAIL/Apo2L)- and CD95 (Fas/APO-1)-induced apoptosis was investigated using four different cell lines (HeLa, HuH-7, Jurkat, and U-937). All four cell lines exhibited different levels of cathepsins and responded differently to apoptosis triggering, with Jurkat cells being the most sensitive and the only ones that were sensitive to the agonistic anti-APO-1 antibody. Apoptosis was accompanied by caspase activation, loss of the mitochondria and lysosome integrity, and the release of cysteine cathepsins into the cytosol, as judged based on the hydrolysis of the cysteine cathepsin substrate benzyloxycarbonyl-Phe-Arg-7-amino-4-methylcoumarin and by the immunological detection of cathepsin B.

Lysosomal pathways to cell death and their therapeutic applications.

Lysosomes are the major cell digestive organelles that were discovered over 50 years ago. They contain a number of hydrolases that help them to degrade intracellular and extracellular material delivered. Among the hydrolases, the cathepsins, a group of proteases enclosed in the lysosomes, have a major role.

Cathepsin cleavage of sirtuin 1 in endothelial progenitor cells mediates stress-induced premature senescence.

Stress-induced premature senescence (SIPS) of endothelial cells (ECs) has emerged as a contributor to global EC dysfunction. One of the cellular abnormalities mechanistically linked to SIPS is lysosomal dysfunction. In this study, we examined the impact of a range of cardiovascular risk factors on the expression of sirtuin 1 (SIRT1), SIPS, and apoptosis, and we documented the role of SIRT1 in reduced EC and endothelial progenitor cell (EPC) viability.