Linked Life Data

10381525

Source:http://linkedlifedata.com/resource/pubmed/id/10381525

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1999-7-23
pubmed:abstractText
Neutrophils undergo constitutive apoptosis when aged ex vivo. Recent studies have indicated roles for Fas/CD95 and the nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase system in this process. We have investigated the role of protein kinase C (PKC) in neutrophil death. We show that there is proteolysis and activation of the novel isoform PKCdelta in aged neutrophils and that this process is accelerated by the addition of an agonistic Fas antibody. PKCdelta proteolysis occurs before the onset of any detectable features of apoptosis and pharmacologic inhibition of this enzyme inhibits neutrophil apoptosis. PKCdelta cleavage and activation is dependent on caspase-8/FADD-like interleukin-1beta converting enzyme (FLICE)-mediated processing of caspase-3/CPP32. Neutrophil survival is prolonged by the addition of broad spectrum (BD.fmk) or caspase-8 targeted (zIETD.fmk) peptide caspase inhibitors. Inhibition of PKCdelta does not prevent apoptosis triggered by factor withdrawal in immature hematopoietic cells, including normal human CD34(+) progenitors indicating that within a given lineage, the mechanisms of apoptosis may be differentiation-stage-specific. Ex vivo aging of neutrophils leads to the increasing production of reactive oxygen species and this is attenuated in cells treated with either caspase or PKCdelta inhibitors. Proteolytically activated PKCdelta acts as a molecular link between the Fas/CD95 receptor and the NADPH-oxidase system and plays a central role in regulating the process of neutrophil apoptosis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Annexin A5, http://linkedlifedata.com/resource/pubmed/chemical/CASP3 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/CASP8 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/CASP9 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Caspase 3, http://linkedlifedata.com/resource/pubmed/chemical/Caspase 8, http://linkedlifedata.com/resource/pubmed/chemical/Caspase 9, http://linkedlifedata.com/resource/pubmed/chemical/Caspases, http://linkedlifedata.com/resource/pubmed/chemical/Isoenzymes, http://linkedlifedata.com/resource/pubmed/chemical/PRKCD protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C, http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C-delta
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0006-4971
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
94
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
291-301
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
Caspase-mediated proteolysis and activation of protein kinase Cdelta plays a central role in neutrophil apoptosis.
pubmed:affiliation
Department of Haematology, University College London Medical School, London, UK. a.khwaja@ucl.ac.uk
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't