Linked Life Data

11299309

Source:http://linkedlifedata.com/resource/pubmed/id/11299309

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2001-4-20
pubmed:abstractText
Emerging evidence supports an important role for caspases in neuronal death following ischemia-reperfusion injury. This study assessed whether cell specific caspases participate in neuronal degeneration and whether caspase inhibition provides neuroprotection following transient retinal ischemia. We utilized a model of transient global retinal ischemia. The spatial and temporal pattern of the active forms of caspase 1, 2 and 3 expression was determined in retinal neurons following ischemic injury. Double-labeling with cell-specific markers identified which cells were expressing different caspases. In separate experiments, animals received various caspase inhibitors before the induction of ischemia. Sixty minutes of ischemia resulted in a delayed, selective neuronal death of the inner retinal layers at 7 days. Expression of caspase 1 was not detected at any time point. Maximal expression of caspase 2 was found at 24 h primarily in the inner nuclear and ganglion cell layers of the retina and localized to ganglion and amacrine neurons. Caspase 3 also peaked at 24 h in both the inner nuclear and outer nuclear layers and was predominantly expressed in photoreceptor cells and to a lesser extent in amacrine neurons. The pan caspase inhibitor, Boc-aspartyl fmk, or an antisense oligonucleotide inhibitor of caspase 2 led to significant histopathologic and functional improvement (electroretinogram) at 7 days. No protection was found with the caspase 1 selective inhibitor, Y-vad fmk. These observations suggest that ischemia-reperfusion injury activates different caspases depending on the neuronal phenotype in the retina and caspase inhibition leads to both histologic preservation and functional improvement. Caspases 2 and 3 may act in parallel in amacrine neurons following ischemia-reperfusion. These results in the retina may shed light on differential caspase specificity in global cerebral ischemia.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0022-3042
pubmed:author
pubmed:issnType
Print
pubmed:volume
77
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
466-75
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:11299309-Amino Acid Chloromethyl Ketones, pubmed-meshheading:11299309-Animals, pubmed-meshheading:11299309-Apoptosis, pubmed-meshheading:11299309-Caspases, pubmed-meshheading:11299309-Cysteine Proteinase Inhibitors, pubmed-meshheading:11299309-Drug Administration Schedule, pubmed-meshheading:11299309-Electroretinography, pubmed-meshheading:11299309-Enzyme Induction, pubmed-meshheading:11299309-Eye Proteins, pubmed-meshheading:11299309-Interneurons, pubmed-meshheading:11299309-Ischemia, pubmed-meshheading:11299309-Male, pubmed-meshheading:11299309-Neurons, pubmed-meshheading:11299309-Ocular Hypertension, pubmed-meshheading:11299309-Oligodeoxyribonucleotides, Antisense, pubmed-meshheading:11299309-Phenotype, pubmed-meshheading:11299309-Premedication, pubmed-meshheading:11299309-Rats, pubmed-meshheading:11299309-Rats, Sprague-Dawley, pubmed-meshheading:11299309-Reperfusion Injury, pubmed-meshheading:11299309-Retinal Diseases, pubmed-meshheading:11299309-Retinal Ganglion Cells, pubmed-meshheading:11299309-Tosylphenylalanyl Chloromethyl Ketone
pubmed:year
2001
pubmed:articleTitle
Cell-specific caspase expression by different neuronal phenotypes in transient retinal ischemia.
pubmed:affiliation
Department of Neurology, Albert Einstein College of Medicine, Bronx, New York, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't