NDLI: PPARdelta-mediated p21/p27 induction via increased CREB-binding protein nuclear translocation in beraprost-induced antiproliferation of murine aortic smooth muscle cells.

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PPARdelta-mediated p21/p27 induction via increased CREB-binding protein nuclear translocation in beraprost-induced antiproliferation of murine aortic smooth muscle cells.

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PPARdelta-mediated p21/p27 induction via increased CREB-binding protein nuclear translocation in beraprost-induced antiproliferation of murine aortic smooth muscle cells.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Sue, Yuh-Mou Chung, Chih-Peng Lin, Heng Chou, Ying Jen, Chih-Yu Li, Hsiao-Fen Chang, Chih-Cheng Juan, Shu-Hui
Description	Country affiliation: Taiwan Author Affiliation: Sue YM ( Department of Nephrology, Taipei Medical University-Wan Fang Hospital, Taipei, Taiwan.)
Abstract	We previously showed that an increase in the peroxisome proliferator-activated receptor-delta (PPARdelta), together with subsequent induction of inducible nitric oxide synthase (iNOS) by beraprost (BPS), inhibits aortic smooth muscle cell proliferation. Herein, we delineated the mechanisms of the antiproliferative effects of BPS through the induction of p21/p27. BPS concentration dependently induced the p21/p27 promoter- and consensus cAMP-responsive element (CRE)-driven luciferase activities, which were significantly suppressed by blocking PPARdelta activation. Surprisingly, other than altering the CRE-binding protein (CREB), BPS-mediated PPARdelta activation increased nuclear localization of the CREB-binding protein (CBP), a coactivator, which was further confirmed by chromatin immunoprecipitation. Furthermore, novel functional PPAR-responsive elements (PPREs) next to CREs in the rat p21/p27 promoter regions were identified, where PPARdelta interacted with CREB through CBP recruitment. BPS-mediated suppression of restenosis in mice with angioplasty was associated with p21/p27 induction. Herein, we demonstrate for the first time that BPS-mediated PPARdelta activation enhances transcriptional activation of p21/p27 by increasing CBP nuclear translocation, which contributes to the vasoprotective action of BPS.
File Format	HTM / HTML
ISSN	03636143
e-ISSN	15221563
Journal	American Journal of Physiology - Cell Physiology
Issue Number	2
Volume Number	297
Language	English
Publisher	American Physiological Society
Publisher Date	2009-08-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Discipline Cell Biology Creb-binding Protein Metabolism Cyclin-dependent Kinase Inhibitor P21 Cyclin-dependent Kinase Inhibitor P27 Epoprostenol Analogs & Derivatives Myocytes, Smooth Muscle Drug Effects Physiology Ppar Delta Vasodilator Agents Pharmacology Active Transport, Cell Nucleus Animals Aorta Cytology Genetics Cell Proliferation Mice Muscle, Smooth, Vascular Rna, Small Interfering Rats, Sprague-dawley Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Cell Biology Physiology

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PPARdelta-mediated p21/p27 induction via increased CREB-binding protein nuclear translocation in beraprost-induced antiproliferation of murine aortic smooth muscle cells.

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