Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
1998-1-26
pubmed:abstractText
Normal lymphocytes are highly sensitive to the damaging effects of ionizing radiation, and undergo cell death by apoptosis. We have investigated the possible involvement of the Interleukin-1 beta-converting enzyme (ICE) (Caspase) protease family, which appears to play an important role as intracellular mediator of apoptosis. Resting B lymphocytes isolated from human peripheral blood were irradiated (6 Gy) and cultured for 24 h, resulting in 25 +/- 5.1% apoptotic cells, as measured by the TUNEL assay (mean +/- SD, n = 6). Addition of the ICE family inhibitor Z-VAD.fmk (50 microM) completely inhibited apoptosis (2.0 +/- 1.5% at 24 h). By using fluorogenic substrates containing the peptide recognition sequences DEVD and YVAD, the type of ICE family protease involved was examined more closely. A marked transient increase in DEVD-, and absent YVAD-cleavage activity indicated the involvement of a CPP32-like protease, not an ICE-like protease. Western blot analysis demonstrated that untreated B lymphocytes expressed the proform of the ICE family members CPP32 and ICH1L, but no detectable ICE. The induction of cell death by radiation was accompanied by the activation of CPP32 as shown by the cleavage of the proform to the active subunit p17, and the cleavage of poly(ADP-ribose) polymerase (PARP), one of the known substrates of CPP32. In contrast, no activation of ICH1L could be detected. These results indicate the involvement of CPP32 and possibly other CPP32-like proteases in radiation-induced apoptosis of resting B lymphocytes.
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/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/Coumarins, http://linkedlifedata.com/resource/pubmed/chemical/Cysteine Endopeptidases, http://linkedlifedata.com/resource/pubmed/chemical/Cysteine Proteinase Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/Oligopeptides, http://linkedlifedata.com/resource/pubmed/chemical/Proteins, http://linkedlifedata.com/resource/pubmed/chemical/benzyloxycarbonyl-aspartyl-glutamyl-..., http://linkedlifedata.com/resource/pubmed/chemical/benzyloxycarbonylvalyl-alanyl-aspart...
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0300-9475
pubmed:author
pubmed:issnType
Print
pubmed:volume
46
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
601-8
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1997
pubmed:articleTitle
Involvement of ICE (Caspase) family in gamma-radiation-induced apoptosis of normal B lymphocytes.
pubmed:affiliation
Department of Immunology, Norwegian Radium Hospital, Oslo, Norway.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't