دورية أكاديمية

Urinary metabolomics in Fxr-null mice reveals activated adaptive metabolic pathways upon bile acid challenge

التفاصيل البيبلوغرافية
العنوان: Urinary metabolomics in Fxr-null mice reveals activated adaptive metabolic pathways upon bile acid challenge
المؤلفون: Joo-Youn Cho, Tsutomu Matsubara, Dong Wook Kang, Sung-Hoon Ahn, Kristopher W. Krausz, Jeffrey R. Idle, Hans Luecke, Frank J. Gonzalez
المصدر: Journal of Lipid Research, Vol 51, Iss 5, Pp 1063-1074 (2010)
بيانات النشر: Elsevier, 2010.
سنة النشر: 2010
المجموعة: LCC:Biochemistry
مصطلحات موضوعية: adaptive response, cholic acid, corticosterone, Cyp3a11, farnesoid X receptor, lithocholic acid, Biochemistry, QD415-436
الوصف: Farnesoid X receptor (FXR) is a nuclear receptor that regulates genes involved in synthesis, metabolism, and transport of bile acids and thus plays a major role in maintaining bile acid homeostasis. In this study, metabolomic responses were investigated in urine of wild-type and Fxr-null mice fed cholic acid, an FXR ligand, using ultra-performance liquid chromatography (UPLC) coupled with electrospray time-of-flight mass spectrometry (TOFMS). Multivariate data analysis between wild-type and Fxr-null mice on a cholic acid diet revealed that the most increased ions were metabolites of p-cresol (4-methylphenol), corticosterone, and cholic acid in Fxr-null mice. The structural identities of the above metabolites were confirmed by chemical synthesis and by comparing retention time (RT) and/or tandem mass fragmentation patterns of the urinary metabolites with the authentic standards. Tauro-3α,6,7α,12α-tetrol (3α,6,7α,12α-tetrahydroxy-5β-cholestan-26-oyltaurine), one of the most increased metabolites in Fxr-null mice on a CA diet, is a marker for efficient hydroxylation of toxic bile acids possibly through induction of Cyp3a11. A cholestatic model induced by lithocholic acid revealed that enhanced expression of Cyp3a11 is the major defense mechanism to detoxify cholestatic bile acids in Fxr-null mice. These results will be useful for identification of biomarkers for cholestasis and for determination of adaptive molecular mechanisms in cholestasis.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 0022-2275
Relation: http://www.sciencedirect.com/science/article/pii/S0022227520410624; https://doaj.org/toc/0022-2275
DOI: 10.1194/jlr.M002923
URL الوصول: https://doaj.org/article/0aab0494e30640c3991b1e89121d7a0b
رقم الأكسشن: edsdoj.0aab0494e30640c3991b1e89121d7a0b
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:00222275
DOI:10.1194/jlr.M002923