Linked Life Data

9056419

Source:http://linkedlifedata.com/resource/pubmed/id/9056419

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1997-3-20
pubmed:abstractText
Biochemical analyses of nuclear apoptosis in vitro have revealed the existence of multiple active interleukin-1beta-converting enzyme-related proteases (caspases) with distinct substrate recognition properties in extracts of preapoptotic chicken DU249 cells (S/M extracts). Previously we demonstrated that the activity of a caspase that cleaves lamins is required for the disintegration of nuclei in the late stages of apoptosis, despite the presence of a second active caspase that cleaves poly(ADP-ribose) polymerase (PARP). One simple explanation for this observation was that the lamin-cleaving caspase is sufficient to drive the nuclear events of apoptotic execution. Here, we report that phenylarsine oxide (PAO) inhibits the protease activities of recombinant human caspases as well as endogenous chicken caspases that are active in S/M extracts. PAO at 100 microM blocks the morphological changes of nuclear apoptosis in vitro and internucleosomal DNA fragmentation in S/M extracts without interfering with PARP or lamin A cleavage. Thus, lamin cleavage is not sufficient to drive the changes in nuclear morphology characteristic of apoptosis. Affinity labeling with YV(bio)KD-aomk shows that the degree of sensitivity to PAO differs among active caspases in S/M extracts. These results suggest that a PAO-sensitive caspase that is distinct from the PARP- or lamin-cleaving enzymes is required for the initiation of apoptotic morphological changes and for the activation of endonuclease(s). Taken together, our results suggest that two or more caspases are required for proteolytic events that are essential for the initiation and completion of nuclear apoptotic changes. The observation that PAO is an inhibitor of caspases and nuclear apoptotic events should be useful for the biochemical dissection of apoptosis in vitro and in vivo.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0014-4827
pubmed:author
pubmed:issnType
Print
pubmed:day
25
pubmed:volume
231
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
123-31
pubmed:dateRevised
2009-9-29
pubmed:meshHeading
pubmed-meshheading:9056419-Affinity Labels, pubmed-meshheading:9056419-Animals, pubmed-meshheading:9056419-Apoptosis, pubmed-meshheading:9056419-Arsenicals, pubmed-meshheading:9056419-Cell Line, pubmed-meshheading:9056419-Cell Nucleus, pubmed-meshheading:9056419-Chickens, pubmed-meshheading:9056419-Cysteine Endopeptidases, pubmed-meshheading:9056419-Cysteine Proteinase Inhibitors, pubmed-meshheading:9056419-DNA Fragmentation, pubmed-meshheading:9056419-HeLa Cells, pubmed-meshheading:9056419-Humans, pubmed-meshheading:9056419-Lamin Type A, pubmed-meshheading:9056419-Lamins, pubmed-meshheading:9056419-Nuclear Proteins, pubmed-meshheading:9056419-Phosphoproteins, pubmed-meshheading:9056419-Phosphorylation, pubmed-meshheading:9056419-Poly(ADP-ribose) Polymerases, pubmed-meshheading:9056419-Recombinant Proteins
pubmed:year
1997
pubmed:articleTitle
Inhibition of ICE-related proteases (caspases) and nuclear apoptosis by phenylarsine oxide.
pubmed:affiliation
Michael Swann Building, The King's Buildings, University of Edinburgh, Mayfield Road, Edinburgh, EH9 3JR, Scotland, United Kingdom.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't