Document Detail


Activation of caspase-3-like enzymes in non-apoptotic T cells.
MedLine Citation:
PMID:  9541584     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The activation of the caspase family of cysteine proteases is a key step in the implementation of apoptotic cell death leading to further downstream effects such as DNA fragmentation. In cultured tumor cells, caspase activity appears only when cells are undergoing apoptosis. Here we show that human and murine T lymphocytes acquire high intracellular activities of cell death-specific caspases upon activation by mitogens and IL-2 without evidence that apoptosis is proceeding. The highest activity is seen when cells are mitogen activated for 3 days. On a per cell basis, caspase activity in activated T cells is much higher than in tumor cells induced to undergo apoptosis. In the presence of exogenously added IL-2 cells stay alive and maintain a high level of caspase activity while IL-2 withdrawal results in cell death and decline of caspase activity. Caspase activity can also be measured in extracts from spleen and lymph nodes from mice injected with superantigen. While in tumor cell lines caspase activity correlates with cleavage of poly(ADP)-ribose polymerase (PARP) and DNA fragmentation, in activated T cells cleavage products of cellular PARP can be detected whereas DNA fragmenting activity appears only upon IL-2 withdrawal which coincides with cell death. These data show that caspase activation in intact cells does not necessarily lead to cell death and argue for a checkpoint in the apoptotic pathway downstream of caspases. Furthermore, they provide a molecular correlate for the high susceptibility of activated T cells for apoptosis.
Authors:
S Wilhelm; H Wagner; G Häcker
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  European journal of immunology     Volume:  28     ISSN:  0014-2980     ISO Abbreviation:  Eur. J. Immunol.     Publication Date:  1998 Mar 
Date Detail:
Created Date:  1998-04-23     Completed Date:  1998-04-23     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  1273201     Medline TA:  Eur J Immunol     Country:  GERMANY    
Other Details:
Languages:  eng     Pagination:  891-900     Citation Subset:  IM    
Affiliation:
Institut für Medizinische Mikrobiologie, Immunologie und Hygiene, Technische Universität München, Germany.
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MeSH Terms
Descriptor/Qualifier:
Animals
Annexin A5 / metabolism
Apoptosis*
Caspase 3
Caspases*
Cells, Cultured
Cysteine Endopeptidases / metabolism*
DNA Fragmentation
Enterotoxins / pharmacology
Enzyme Activation
Female
Humans
Interleukin-2 / pharmacology
Lymphocyte Activation*
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Phosphatidylserines / metabolism
Poly(ADP-ribose) Polymerases
Proteins / metabolism
T-Lymphocytes / enzymology*
Up-Regulation
Chemical
Reg. No./Substance:
0/Annexin A5; 0/Enterotoxins; 0/Interleukin-2; 0/Phosphatidylserines; 0/Proteins; 39424-53-8/enterotoxin B, staphylococcal; EC 2.4.2.30/PARP1 protein, human; EC 2.4.2.30/Parp1 protein, mouse; EC 2.4.2.30/Poly(ADP-ribose) Polymerases; EC 3.4.22.-/CASP3 protein, human; EC 3.4.22.-/Casp3 protein, mouse; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspases; EC 3.4.22.-/Cysteine Endopeptidases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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