Linked Life Data

15689952

Source:http://linkedlifedata.com/resource/pubmed/id/15689952

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2005-3-24
pubmed:abstractText
It is well established that tissue damage and functional outcome after experimental or clinical stroke are shaped by biologic sex. We investigated the novel hypothesis that ischemic cell death from neuronally derived nitric oxide (NO) or poly-ADP ribose polymerase (PARP-1) activation is sexually dimorphic and that interruption of these molecular death pathways benefits only the male brain. Female neuronal nitric oxide synthase (nNOS) knockout (nNOS-/-) mice exhibited exacerbated histological injury after middle cerebral artery occlusion (MCAO) relative to wild-type (WT) females, unlike the protection observed in male nNOS-/- littermates. Similarly, treatment with the nNOS inhibitor (7-nitroindozole, 25 mg/kg) increased infarction in female C57Bl6 WT mice, but protected male mice. The mechanism for this sexually specific response is not mediated through changes in protein expression of endothelial NOS or inducible NOS, or differences in intraischemic cerebral blood flow. Unlike male PARP-1 knockouts (PARP1-/-), female PARP1-/- littermates sustained grossly increased ischemic damage relative to sex-matched WT mice. Treatment with a PARP inhibitor (PJ-34, 10 mg/kg) resulted in identical results. Loss of PARP-1 resulted in reversal of the neuroprotective activity by the female sex steroid, 17beta estradiol. These data suggest that the previously described cell death pathways involving NO and PARP ischemic neurotoxicity may be operant solely in male brain and that the integrity of nNO/PARP-1 signaling is paradoxically protective in the female.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0271-678X
pubmed:author
pubmed:issnType
Print
pubmed:volume
25
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
502-12
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:15689952-Animals, pubmed-meshheading:15689952-Blotting, Western, pubmed-meshheading:15689952-Brain Ischemia, pubmed-meshheading:15689952-Cerebrovascular Circulation, pubmed-meshheading:15689952-Enzyme Inhibitors, pubmed-meshheading:15689952-Estradiol, pubmed-meshheading:15689952-Female, pubmed-meshheading:15689952-Isoenzymes, pubmed-meshheading:15689952-Male, pubmed-meshheading:15689952-Mice, pubmed-meshheading:15689952-Mice, Knockout, pubmed-meshheading:15689952-Nerve Tissue Proteins, pubmed-meshheading:15689952-Nitric Oxide, pubmed-meshheading:15689952-Nitric Oxide Synthase, pubmed-meshheading:15689952-Nitric Oxide Synthase Type I, pubmed-meshheading:15689952-Ovariectomy, pubmed-meshheading:15689952-Oxidative Stress, pubmed-meshheading:15689952-Poly(ADP-ribose) Polymerases, pubmed-meshheading:15689952-Reperfusion Injury, pubmed-meshheading:15689952-Sex Characteristics, pubmed-meshheading:15689952-Signal Transduction
pubmed:year
2005
pubmed:articleTitle
Ischemic nitric oxide and poly (ADP-ribose) polymerase-1 in cerebral ischemia: male toxicity, female protection.
pubmed:affiliation
Department of Neurology, University of Connecticut Health Center, Farmington, Connecticut 06030-1840, USA. lmccullough@uchc.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't