Involvement of lysosomal cathepsins in the cleavage of DNA topoisomerase I during necrotic cell death

Abstract

Objective. Autoantibodies to DNA topoisomerase I (topo I) are associated with diffuse systemic sclerosis (SSc), appear to be antigen driven, and may be triggered by cryptic epitopes exposed during in vivo topo I fragmentation. These autoantibodies recognize topo I and fragments of this autoantigen generated during apoptosis and necrosis. We undertook this study to determine whether lysosomal cathepsins are involved in topo I fragmentation during necrosis.Methods. Topo I cleavage during necrosis was assessed by immunoblotting of lysates from L929 fibroblasts exposed to tumor necrosis factor ␣ (

Necroptosis, necrosis and secondary necrosis converge on similar cellular disintegration features

“…However, in extreme cases of extensive apoptosis and insufficient phagocytic capacity in vivo, it may have a (patho)physiological role. Lysosomal disintegration leading to the release of cathepsins, and oxidative burst may participate in the generation of modified damage-associated molecular patterns (DAMPs) through proteolysis 37 and generation of oxidized products. 38 In that respect, the cellular disintegration phase serves as a last life-buoy to attract immune competent cells and to initiate regeneration processes.…”

Abundantly expressed transcripts in the lymphoid organ of the black tiger shrimp, Penaeus monodon, and their implication in immune function

“…However, the cathepsin family, including cathepsins B, D and L, has additionally been reported to be involved in apoptosis [25][26][27]. In this light it is interesting that Robalino et al [28] reported that in L. vannamei several cathepsins, particularly cathepsin L, were present in cDNA libraries of hemocyte, gill and hepatopancreas enriched for transcripts induced by WSSV infection and by dsRNA, an inducer of antiviral immunity in shrimp.…”

Nuclear translocation of mitochondrial cytochrome c, lysosomal cathepsins B and D, and three other death‐promoting proteins within the first 60 minutes of generalized seizures

“…Release of lysosomal enzymes with subsequent cellular necrosis or apoptosis has been described in nonneuronal cell culture (Zhao et al, 2003;Pacheco et al, 2005). In Caenorhabditis elegans, aspartyl and calpain proteases are required for necrotic cell death (Syntichaki et al, 2002), as is the vacuolar H 1 -ATPase, a pump that acidifies lysosomes and is responsible for the drop in cytoplasmic pH that occurs in cellular necrosis (Syntichaki et al, 2005).…”