Source:http://linkedlifedata.com/resource/pubmed/id/19640904
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
4
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pubmed:dateCreated |
2009-9-29
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pubmed:abstractText |
Prostacyclin and peroxisome proliferator-activated receptors (PPAR) protect against ischemia-reperfusion (I/R) injury by the induction of an anti-inflammatory pathway. In this study, we examined the prostacyclin-enhanced protective effect of PPARalpha in I/R-induced kidney injury. PPAR-alpha reduced the NF-kappaB-induced overexpression of TNF-alpha and apoptosis in cultured kidney cells. In a murine model, pretreating wild-type (WT) mice with a PPAR-alpha activator, docosahexaenoic acid (DHA), significantly reduced I/R-induced renal dysfunction (lowered serum creatinine and urea nitrogen levels), apoptotic responses (decreased apoptotic cell number and caspase-3, -8 activation), and NF-kappaB activation. By comparison, I/R-induced injury was exacerbated in PPAR-alpha knockout mice. This indicated that PPAR-alpha attenuated renal I/R injury via NF-kappaB-induced TNF-alpha overexpression. Overexpression of prostacyclin using an adenovirus could also induce PPAR-alpha translocation from the cytosol into the nucleus to inhibit caspase-3 activation. This prostacyclin/PPAR-alpha pathway attenuated TNF-alpha promoter activity by binding to NF-kappaB. Using a cAMP inhibitor (CAY10441) and a prostacyclin receptor antibody, we also found that there was another prostacyclin/IP receptor/cAMP pathway that could inhibit TNF-alpha production. Taken together, our results demonstrate for the first time that prostacyclin induces the translocation of PPAR-alpha from the cytosol into the nucleus and attenuates NF-kappaB-induced TNF-alpha activation following renal I/R injury. Treatments that can augment prostacyclin, PPAR-alpha, or the associated signaling pathways may ameliorate conditions associated with renal I/R injury.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Docosahexaenoic Acids,
http://linkedlifedata.com/resource/pubmed/chemical/Epoprostenol,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/PPAR alpha,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
1522-1466
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:volume |
297
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
F1109-18
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pubmed:dateRevised |
2011-4-28
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pubmed:meshHeading |
pubmed-meshheading:19640904-Animals,
pubmed-meshheading:19640904-Cells, Cultured,
pubmed-meshheading:19640904-Docosahexaenoic Acids,
pubmed-meshheading:19640904-Epoprostenol,
pubmed-meshheading:19640904-Kidney Function Tests,
pubmed-meshheading:19640904-Male,
pubmed-meshheading:19640904-Mice,
pubmed-meshheading:19640904-NF-kappa B,
pubmed-meshheading:19640904-PPAR alpha,
pubmed-meshheading:19640904-Rats,
pubmed-meshheading:19640904-Reperfusion Injury,
pubmed-meshheading:19640904-Tumor Necrosis Factor-alpha
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pubmed:year |
2009
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pubmed:articleTitle |
Prostacyclin-induced peroxisome proliferator-activated receptor-alpha translocation attenuates NF-kappaB and TNF-alpha activation after renal ischemia-reperfusion injury.
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pubmed:affiliation |
Graduate Institute of Clinical Medicine, College of Medicine, Taipai Medical University, Taiwan.
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pubmed:publicationType |
Journal Article
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