Linked Life Data

15729291

Source:http://linkedlifedata.com/resource/pubmed/id/15729291

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2005-6-23
pubmed:abstractText
Cerebral ischemia-reperfusion leads to vascular dysfunction characterized by endothelial cell injury or death. In the present study, we used an in vitro model to elucidate mechanisms of human brain microvascular endothelial cell (HBMEC) injury after episodic ischemia-reperfusion. Near-confluent HBMEC cultures were exposed to intermittent hypoxia-reoxygenation (HX/RO) and, at different recovery time points, cell viability was assessed by the MTT assay, apoptotic death by fluorescence microscopy of terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate-biotin nick end labeling (TUNEL)-positive cells, and nuclear translocation of apoptosis-inducing factor (AIF) and cleavage of poly(ADP-ribose) polymerase-1 (PARP-1) by immunoblotting of subcellular fractions. Reductions in HBMEC viability were proportional to the number of HX/RO cycles, and not the total duration of hypoxia. Using four cycles of 1-h HX with 1 h of intervening normoxic RO, cell viability was reduced 30% to 40% between 12 and 48 h. Treatment with the PARP-1 inhibitors 3-aminobenzamide or 4-amino-1,8-naphthalimide during the insult improved HBMEC viability at 24 h after insult, and resulted in dose-dependent reductions in TUNEL-positivity at 16 h after insult, but not if these treatments were delayed by 4 h. HX/RO-induced increases in nuclear AIF translocation, as well as PARP-1 cleavage, were also reduced dose-dependently at 4 h after insult by the inhibitors. The caspase inhibitor z-VAD-fmk blocked PARP-1 cleavage, but did not affect AIF translocation and was only modestly cytoprotective. These findings indicate that PARP-1 activation and a PARP-1-dependent, caspase-independent, nuclear translocation of AIF contribute to apoptotic cerebral endothelial cell death after ischemia-reperfusion, underscoring the potential for ischemic microvascular protection by inhibiting PARP activation or preventing AIF translocation.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0271-678X
pubmed:author
pubmed:issnType
Print
pubmed:volume
25
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
868-77
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Cerebral endothelial cell apoptosis after ischemia-reperfusion: role of PARP activation and AIF translocation.
pubmed:affiliation
Department of Neurosurgery, Washington University School of Medicine, St Louis, Missouri 63110, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, N.I.H., Extramural