PMID- 25927246 OWN - NLM STAT- MEDLINE DCOM- 20161013 LR - 20190116 IS - 1029-2403 (Electronic) IS - 1026-8022 (Linking) VI - 57 IP - 1 DP - 2016 TI - Features of cell death, mitochondrial activation and caspase dependence of rabbit anti-T-lymphocyte globulin signaling in lymphoblastic Jurkat cells are distinct from classical apoptosis signaling of CD95. PG - 177-82 LID - 10.3109/10428194.2015.1044449 [doi] AB - Rabbit anti-T-lymphocyte-globulin (ATG) is used for immunosuppression in organ and stem cell transplantation. The aim of this study was to investigate ATG-induced cell death compared to CD95-signaling of apoptosis. We measured features of cell death at the cell membrane, mitochondria, nuclei and caspase-3 cleavage. We used the following inhibitors: the caspase inhibitor N-benzyloxycarbonyl-Val-Ala-Asp (O-Me)-fluoromethyl ketone (zVAD-fmk), the serine protease inhibitors 3,4 dichloroisocoumarin (DCI) and N-alpha-tosyl-L-lysinyl-chloromethylketone (TLCK) and the reducing agent N-acetycysteine (NAC). ATG-induced cellular changes were rapid, included mitochondrial membrane permeability (MMP) induction and annexin V/propidium iodide (PI) positivity but little caspase-3 activation and nuclear morphology changes. MMP was not sensitive to caspase inhibition, serine protease inhibition with DCI moderately reduced MMP. These findings were in contrast to CD95-signaling. Interestingly, TLCK massively augmented CD95-induced MMP which could be abrogated by NAC. In conclusion, ATG-signaling differs in features and kinetics from CD95-induced apoptosis with caspase-independent mechanisms involved in MMP. FAU - Ziegler, Christian AU - Ziegler C AD - a Department of Medical Oncology , National Center for Tumor Diseases, Heidelberg University Hospital , Heidelberg , Germany. AD - b Department of Hematology and Oncology , Albert Ludwigs-University Medical Center Freiburg , Freiburg , Germany. AD - c Department of Hematology and Oncology , Charite Medical Center Berlin , Campus Virchow Klinik, Berlin, Germany. FAU - Finke, Jurgen AU - Finke J AD - b Department of Hematology and Oncology , Albert Ludwigs-University Medical Center Freiburg , Freiburg , Germany. FAU - Grullich, Carsten AU - Grullich C AD - a Department of Medical Oncology , National Center for Tumor Diseases, Heidelberg University Hospital , Heidelberg , Germany. AD - b Department of Hematology and Oncology , Albert Ludwigs-University Medical Center Freiburg , Freiburg , Germany. LA - eng PT - Journal Article DEP - 20150525 PL - United States TA - Leuk Lymphoma JT - Leukemia & lymphoma JID - 9007422 RN - 0 (Antilymphocyte Serum) RN - 0 (fas Receptor) RN - EC 3.4.22.- (Caspase 3) RN - EC 3.4.22.- (Caspases) RN - EC 3.4.24.- (Matrix Metalloproteinases) SB - IM MH - Animals MH - Antilymphocyte Serum/*pharmacology MH - Apoptosis/*drug effects MH - Caspase 3/metabolism MH - Caspases/*metabolism MH - Cell Membrane Permeability MH - Humans MH - Jurkat Cells MH - Matrix Metalloproteinases/metabolism MH - Mitochondria/*drug effects/*metabolism MH - Mitochondrial Membranes/metabolism MH - Rabbits MH - Signal Transduction/*drug effects MH - fas Receptor/*metabolism OTO - NOTNLM OT - CD95 OT - Caspase OT - Jurkat OT - rabbit anti-T-lymphocyte-globulin (ATG) OT - reactive oxygen species (ROS) OT - serine protease EDAT- 2015/05/01 06:00 MHDA- 2016/10/14 06:00 CRDT- 2015/05/01 06:00 PHST- 2015/05/01 06:00 [entrez] PHST- 2015/05/01 06:00 [pubmed] PHST- 2016/10/14 06:00 [medline] AID - 10.3109/10428194.2015.1044449 [doi] PST - ppublish SO - Leuk Lymphoma. 2016;57(1):177-82. doi: 10.3109/10428194.2015.1044449. Epub 2015 May 25.