rdf:type |
|
lifeskim:mentions |
|
pubmed:issue |
1-2
|
pubmed:dateCreated |
2003-7-1
|
pubmed:abstractText |
Poly(ADP-ribose) is synthesized from nicotinamide adenine dinucleotide (NAD(+)) by poly(ADP-ribose) polymerase (PARP) and degraded by poly(ADP-ribose) glycohydrolase (PARG). Overactivation of the poly(ADP-ribose) pathway increases nicotinamide and decreases cellular NAD(+)/ATP, which leads to cell death. Blocking poly(ADP-ribose) metabolism by inactivating PARP has been shown to reduce ischemia injury. We investigated whether disrupting the poly(ADP-ribose) cycle by PARG inhibition could achieve similar protection. We demonstrate that either pre- or post-ischemia treatment with 40 mg/kg of N-bis-(3-phenyl-propyl)9-oxo-fluorene-2,7-diamide, a novel PARG inhibitor, significantly reduces brain infarct volumes by 40-53% in a rat model of focal cerebral ischemia. Our result provides the first evidence that PARG inhibitors can ameliorate ischemic brain damage in vivo, in support of PARG as a new therapeutic target for treating ischemia injury.
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pubmed:language |
eng
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pubmed:journal |
|
pubmed:citationSubset |
IM
|
pubmed:chemical |
|
pubmed:status |
MEDLINE
|
pubmed:month |
Jul
|
pubmed:issn |
0006-8993
|
pubmed:author |
|
pubmed:issnType |
Print
|
pubmed:day |
18
|
pubmed:volume |
978
|
pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
|
pubmed:pagination |
99-103
|
pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:12834903-Animals,
pubmed-meshheading:12834903-Brain,
pubmed-meshheading:12834903-Brain Ischemia,
pubmed-meshheading:12834903-Cerebral Infarction,
pubmed-meshheading:12834903-Coloring Agents,
pubmed-meshheading:12834903-Diamide,
pubmed-meshheading:12834903-Enzyme Inhibitors,
pubmed-meshheading:12834903-Glycoside Hydrolases,
pubmed-meshheading:12834903-Infarction, Middle Cerebral Artery,
pubmed-meshheading:12834903-Male,
pubmed-meshheading:12834903-Rats,
pubmed-meshheading:12834903-Rats, Sprague-Dawley,
pubmed-meshheading:12834903-Reperfusion,
pubmed-meshheading:12834903-Tetrazolium Salts,
pubmed-meshheading:12834903-Time Factors
|
pubmed:year |
2003
|
pubmed:articleTitle |
Post-treatment with a novel PARG inhibitor reduces infarct in cerebral ischemia in the rat.
|
pubmed:affiliation |
Guilford Pharmaceuticals Inc, 6611 Tributary Street, Baltimore, MD 21224, USA.
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pubmed:publicationType |
Journal Article,
Comparative Study
|