کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5824153 | 1118430 | 2009 | 11 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Poly(ADP-ribose) polymerase-1 (PARP-1) transcriptionally regulates angiotensin AT2 receptor (AT2R) and AT2R binding protein (ATBP) genes
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کلمات کلیدی
PARP-1TBPRASMEFsAT1RRenin–angiotensin system (RAS)AT2RPLZFSHP-1RLAATIPTATA box-binding protein - TATA جعبه اتصال پروتئینPar - توسطRenin–angiotensin system - سیستم رنین-آنژیوتانسینrelative luciferase activity - فعالیت لوکیفراز نسبیmouse embryonic fibroblasts - موش فیبروبلاست جنینیPromoter - پروموترPoly(ADP-ribose) - پلی (ADP-ribose)Poly(ADP-ribose) polymerase-1 - پلی (ADP-ribose) پلیمراز-1CHiP - چیپchromatin-immunoprecipitation - کروماتین-ایمن سازیAngiotensin AT2 receptor - گیرنده آنژیوتانسین AT2Angiotensin AT1 receptor - گیرنده آنیوتانسین AT1
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
داروشناسی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
The renin-angiotensin system (RAS) plays a crucial role in cardiovascular and neuronal (patho-)physiology. The angiotensin AT2 receptor (AT2R) seems to counteract the proinflammatory, prohypertrophic and profibrotic actions of the AT1 receptor. Recently, we identified a novel protein, termed “AT2R binding protein” (ATBP/ATIP) which seems essential for AT2R-mediated growth inhibition. Poly(ADP-ribose) polymerase-1 (PARP-1) can act as a nuclear integrator of angiotensin II-mediated cell signalling, and has been implicated in the pathogenesis of cardiovascular and neuronal disease.In this study, promoters of human AT2R and ATIP1 were cloned and two transcriptional start sites in the ATIP1 promoter were identified whereas only one was detected in the AT2R promoter. Promoter assays indicated that the exon 1-intron 1 region of AT2R is necessary and sufficient for AT2R promoter activity. Inverse cloning experiments indicated that this regulatory region is a promoter but not an enhancer element implicating (a) further start site(s) in this region. Consistently, the exon 1-intron 1 region of AT2R was shown to tether the basal transcriptional machinery. Overexpression, pharmacological inhibition and ablation of PARP demonstrated that PARP-1 activates the ATIP1 gene but represses the AT2R on promoter and mRNA levels in vitro, and in brain tissue in vivo. Additional experiments indicated that AT2R activation does not modulate PARP-1 transcript levels but increases AT2R promoter activity, thereby creating a positive feedback mechanism.Our results demonstrate that PARP-1 acts as novel node within the RAS network based on its ability to regulate downstream targets such as AT2R and its adapter protein ATBP.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical Pharmacology - Volume 77, Issue 12, 15 June 2009, Pages 1795-1805
Journal: Biochemical Pharmacology - Volume 77, Issue 12, 15 June 2009, Pages 1795-1805
نویسندگان
Jana Reinemund, Kerstin Seidel, Ulrike M. Steckelings, Daniela Zaade, Sabrina Klare, Franziska Rompe, Marlen Katerbaum, Jens Schacherl, Yaosi Li, Mario Menk, Jan H. Schefe, Petra Goldin-Lang, Csaba Szabo, Gabor Olah, Thomas Unger, Heiko Funke-Kaiser,