Linked Life Data

9925765

Source:http://linkedlifedata.com/resource/pubmed/id/9925765

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1999-3-15
pubmed:abstractText
It is now well established that the caspases, a family of cysteine proteases, play a key role in apoptosis. Although overexpressing each of the caspases in cells triggered apoptosis, the precise role and contribution of individual caspases are still unclear. Caspase-1, the first caspase discovered, was initially implicated in mammalian apoptosis because of its similarity to the gene product ced-3. Using whole cells as well as an in vitro system to study apoptosis, the role of caspase-1 in Fas-mediated apoptosis in Jurkat T cells was examined in greater detail. Using various peptide-based caspase inhibitors, our results showed that N-acetyl-Tyr-Val-Ala-Asp chloromethyl ketone and benzyloxycarbonyl-Val-Ala-Asp (OMe) fluoromethyl ketone efficiently blocked Fas-mediated apoptosis in Jurkat T cells, whereas N-acetyl-Tyr-Val-Ala-Asp aldehyde, which is more specific for caspase-1, had little effect. Cell lysates derived from anti-Fas-stimulated cells, which readily induced apoptotic nuclei morphology and DNA fragmentation in isolated thymocyte nuclei, had no caspase-1 activity using proIL-1beta as a substrate. Time-course studies showed no caspase-1 activity during the activation of apoptosis in Jurkat cells by agonistic Fas antibodies. Furthermore, no pro-caspase-1 protein nor activated form of the protein was detected in normal or apoptotic Jurkat cells. In contrast, both caspase-2 and caspase-3 were readily detected as proenzymes in control cells and their activated forms were detected in apoptotic cells. Incubation of recombinant active caspase-1 with control cell lysates did not activate the apoptotic cascade as shown by the lack of detectable apoptotic nuclei promoting activity using isolated nuclei as substrate. However, under similar conditions proIL-1beta was readily processed into the mature cytokine, indicating that the recombinant caspase-1 remained active in the presence of control cell lysates. Taken together our results demonstrate that caspase-1 is not required for the induction of apoptosis in Jurkat T cells mediated by the Fas antigen.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Amino Acid Chloromethyl Ketones, http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD95, http://linkedlifedata.com/resource/pubmed/chemical/CASP3 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Caspase 1, http://linkedlifedata.com/resource/pubmed/chemical/Caspase 2, http://linkedlifedata.com/resource/pubmed/chemical/Caspase 3, http://linkedlifedata.com/resource/pubmed/chemical/Caspases, http://linkedlifedata.com/resource/pubmed/chemical/Cysteine Proteinase Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-1, http://linkedlifedata.com/resource/pubmed/chemical/L 709049, http://linkedlifedata.com/resource/pubmed/chemical/Oligopeptides, http://linkedlifedata.com/resource/pubmed/chemical/Protein Precursors, http://linkedlifedata.com/resource/pubmed/chemical/benzyloxycarbonylvalyl-alanyl-aspart...
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0014-4827
pubmed:author
pubmed:copyrightInfo
Copyright 1999 Academic Press.
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
246
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
491-500
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
Caspase-1 is not involved in CD95/Fas-induced apoptosis in Jurkat T cells.
pubmed:affiliation
Center for Mechanisms of Human Toxicity, Medical Research Council Toxicology Unit, Leicester University, Hodgkin Building, Lancaster Road, Leicester, LE1 9HN, United Kingdom. scc7@le.ac.uk
pubmed:publicationType
Journal Article