HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 297/4/F1109    most recent 00057.2009v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Chen, H.-H. Articles by Lin, H. PubMed PubMed Citation Articles by Chen, H.-H. Articles by Lin, H.

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

¹Graduate Institute of Clinical Medicine, College of Medicine, Taipai Medical University, and ; ²Department of Internal Medicine, Taipei Medical University Hospital, Taipei; ; ³Graduate Institute of Pharmacology and Toxicology, Tzu Chi University, Hualien; and ; ⁴Institute of Biomedical Sciences, Academia, Sinica, Taiwan

Submitted February 5, 2009 ; accepted in final form July 21, 2009

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 PPAR in I/R-induced kidney injury. PPAR- reduced the NF-B-induced overexpression of TNF- and apoptosis in cultured kidney cells. In a murine model, pretreating wild-type (WT) mice with a PPAR- 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-B activation. By comparison, I/R-induced injury was exacerbated in PPAR- knockout mice. This indicated that PPAR- attenuated renal I/R injury via NF-B-induced TNF- overexpression. Overexpression of prostacyclin using an adenovirus could also induce PPAR- translocation from the cytosol into the nucleus to inhibit caspase-3 activation. This prostacyclin/PPAR- pathway attenuated TNF- promoter activity by binding to NF-B. 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- production. Taken together, our results demonstrate for the first time that prostacyclin induces the translocation of PPAR- from the cytosol into the nucleus and attenuates NF-B-induced TNF- activation following renal I/R injury. Treatments that can augment prostacyclin, PPAR-, or the associated signaling pathways may ameliorate conditions associated with renal I/R injury.

arachidonic acid; IP receptor; cAMP; docosahexaenoic acid; caspase