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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

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 cas...

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Bibliographic Details
Main Authors: Ziegler, Christian Martin (Author) , Finke, Jürgen (Author) , Grüllich, Carsten (Author)
Format: Article (Journal)
Language:English
Published: 2016
In: Leukemia and lymphoma
Year: 2015, Volume: 57, Issue: 1, Pages: 177-182
ISSN:1029-2403
DOI:10.3109/10428194.2015.1044449
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.3109/10428194.2015.1044449
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Author Notes:Christian Ziegler, Jürgen Finke, Carsten Grüllich
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Summary: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.
Item Description:Gesehen am 20.08.2020
Published online: 25 May 2015
Physical Description:Online Resource
ISSN:1029-2403
DOI:10.3109/10428194.2015.1044449

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