Gene interactions and pathways from curated databases and text-mining
American journal of physiology. Renal physiology 2009, PMID: 19640904

Prostacyclin-induced peroxisome proliferator-activated receptor-alpha translocation attenuates NF-kappaB and TNF-alpha activation after renal ischemia-reperfusion injury.

Chen, Hsi-Hsien; Chen, Tzen-Wen; Lin, Heng

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.

Diseases/Pathways annotated by Medline MESH: Reperfusion Injury
Document information provided by NCBI PubMed

Text Mining Data

TNF-alpha ⊣ NF-kappaB: " PPAR-alpha reduced the NF-kappaB induced overexpression of TNF-alpha and apoptosis in cultured kidney cells "

TNF-alpha → PPAR-alpha: " PPAR-alpha reduced the NF-kappaB induced overexpression of TNF-alpha and apoptosis in cultured kidney cells "

TNF-alpha → NF-kappaB: " This indicated that PPAR-alpha attenuated renal I/R injury via NF-kappaB induced TNF-alpha overexpression "

caspase-3 ⊣ PPAR-alpha: " Overexpression of prostacyclin using an adenovirus could also induce PPAR-alpha translocation from the cytosol into the nucleus to inhibit caspase-3 activation "

TNF-alpha → NF-kappaB: " 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 "

Manually curated Databases

No curated data.