دورية أكاديمية
أعرض في EDS

X-box binding protein 1 regulates brain natriuretic peptide through a novel AP1/CRE-like element in cardiomyocytes.

التفاصيل البيبلوغرافية
العنوان: X-box binding protein 1 regulates brain natriuretic peptide through a novel AP1/CRE-like element in cardiomyocytes.
المؤلفون: Sawada T; Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan., Minamino T, Fu HY, Asai M, Okuda K, Isomura T, Yamazaki S, Asano Y, Okada K, Tsukamoto O, Sanada S, Asanuma H, Asakura M, Takashima S, Kitakaze M, Komuro I
المصدر: Journal of molecular and cellular cardiology [J Mol Cell Cardiol] 2010 Jun; Vol. 48 (6), pp. 1280-9. Date of Electronic Publication: 2010 Feb 17.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Academic Press Country of Publication: England NLM ID: 0262322 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1095-8584 (Electronic) Linking ISSN: 00222828 NLM ISO Abbreviation: J Mol Cell Cardiol Subsets: MEDLINE
أسماء مطبوعة: Original Publication: London, New York, Academic Press.
مواضيع طبية MeSH: Gene Expression Regulation*, DNA-Binding Proteins/*metabolism , Myocytes, Cardiac/*cytology , Natriuretic Peptide, Brain/*biosynthesis , Transcription Factor AP-1/*metabolism , Transcription Factors/*metabolism, Animals ; Endoplasmic Reticulum Chaperone BiP ; Heat-Shock Proteins/metabolism ; Humans ; Microscopy, Confocal/methods ; Myocardium/metabolism ; Promoter Regions, Genetic ; RNA Interference ; Rats ; Regulatory Factor X Transcription Factors ; X-Box Binding Protein 1
مستخلص: The unfolded protein response (UPR) is triggered to assist protein folding when endoplasmic reticulum (ER) function is impaired. Recent studies demonstrated that ER stress can also induce cell-specific genes. In this study, we examined whether X-box binding protein 1 (XBP1), a major UPR-linked transcriptional factor, regulates the expression of brain natriuretic peptide (BNP) in cardiomyocytes. In samples from failing human hearts, extensive splicing of XBP1 was observed along with increased expression of glucose-regulated protein of 78 kDa (GRP78), a target of spliced XBP1 (sXBP1), suggesting that the UPR was induced in heart failure in humans. Interestingly, quantitative real-time PCR revealed a positive correlation between cardiac expression of GRP78 and BNP, leading us to test the hypothesis that sXBP1 regulates BNP as well as GRP78 in cardiomyocytes. A pharmacological ER stressor caused a dose-dependent increase in the expression of sXBP1 and BNP by cultured cardiomyocytes. Short interfering RNA targeting XBP1 suppressed the induction of BNP expression by a pharmacological ER stressor or norepinephrine, which was rescued by the adenovirus-mediated overexpression of sXBP1. The promoter assay with overexpression of sXBP1 or norepinephrine showed that the proximal AP1/CRE-like element in the promoter region of BNP was critical for transcriptional regulation of BNP by sXBP1. Direct binding of sXBP1 to this element was confirmed by the chromatin immunoprecipitation assay. These findings suggest that ER stress observed in failing hearts regulates cardiac BNP expression through a novel promoter region of the AP1/CRE-like element.
((c) 2010 Elsevier Ltd. All rights reserved.)
المشرفين على المادة: 0 (DNA-Binding Proteins)
0 (Endoplasmic Reticulum Chaperone BiP)
0 (GRP78 protein, rat)
0 (HSPA5 protein, human)
0 (Heat-Shock Proteins)
0 (Regulatory Factor X Transcription Factors)
0 (Transcription Factor AP-1)
0 (Transcription Factors)
0 (X-Box Binding Protein 1)
0 (XBP1 protein, human)
0 (Xbp1 protein, rat)
114471-18-0 (Natriuretic Peptide, Brain)
تواريخ الأحداث: Date Created: 20100223 Date Completed: 20101116 Latest Revision: 20211203
رمز التحديث: 20221213
DOI: 10.1016/j.yjmcc.2010.02.004
PMID: 20170659
قاعدة البيانات: MEDLINE
الوصف
تدمد:1095-8584
DOI:10.1016/j.yjmcc.2010.02.004