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Involvement of lysosomal cathepsins in the cleavage of DNA topoisomerase I during necrotic cell death by Fabio J. Pacheco; Jacqueline Servin; David Dang; Jim Kim; Christine Molinaro; Tracy Daniels; Terry A. Brown‐Bryan; Mizue Imoto‐Egami; Carlos A. Casiano is a Medicine article available to read on EtoBox.
What is Involvement of lysosomal cathepsins in the cleavage of DNA topoisomerase I during necrotic cell death about?
## 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 α (TNFα) and the broad caspase inhibitor Z‐VAD‐FMK, and by immunoblotting of lysates from endothelial cells treated with HgCl~2~. Purified topo I and L929 nuclei were incubated with cathepsins B, D, G, H, and L, and topo I cleavage was detected by immunoblotting. The intracellular localization of cathepsin L activity and topo I in necrotic cells was examined using fluorescence microscopy. ## Results Treatment of L929 cells with TNFα and Z‐VAD‐FMK induced caspase‐independent cell death with necrotic morphology. This cell death involved topo I cleavage into fragments of approximate
Who reads Involvement of lysosomal cathepsins in the cleavage of DNA topoisomerase I during necrotic cell death?
It is typically read by researchers, students, and practitioners in Medicine.
- Author
- Fabio J. Pacheco; Jacqueline Servin; David Dang; Jim Kim; Christine Molinaro; Tracy Daniels; Terry A. Brown‐Bryan; Mizue Imoto‐Egami; Carlos A. Casiano
- Publisher
- John Wiley and Sons; Wiley (John Wiley & Sons); John Wiley & Sons Inc.; Wiley (ISSN 0004-3591)
- Published
- 2005
- Language
- EN
- Field
- Medicine (Health Sciences)