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Title: Regulation of human class I alcohol dehydrogenases by bile acids
Author: Langhi, Cédric
Pedraz-Cuesta, Elena
Haro Bautista, Diego
Marrero González, Pedro F.
Rodríguez Rubio, Joan Carles
Keywords: Regulació genètica
Àcids biliars
Genetic regulation
Bile acids
Issue Date: 16-Jun-2013
Publisher: American Society for Biochemistry and Molecular Biology
Abstract: Class I alcohol dehydrogenases (ADH1s) are the rate-limiting enzymes for ethanol and vitamin A (retinol) metabolism in the liver . Because previous studies have shown that human ADH1 enzymes may participate in bile acid metabolism, we investigated whether the bile acid-activated nuclear receptor farnesoid X receptor (FXR) regulates ADH1 genes. In human hepatocytes, both the endogenous FXR ligand chenodeoxycholic acid and synthetic FXR-specific agonist GW4064 increased ADH1 mRNA, protein, and activity. Moreover, overexpression of a constitutively active form of FXR induced ADH1A and ADH1B expression, whereas silencing of FXR abolished the effects of FXR agonists on ADH1 expression and activity. Transient transfection studies and electrophoretic mobility shift assays revealed functional FXR response elements in the ADH1A and ADH1B proximal promoters, thus indicating that both genes are direct targets of FXR. These findings provide the first evidence for direct connection of bile acid signaling and alcohol metabolism.
Note: Versió postprint del document publicat a:
It is part of: Journal of Lipid Research, 2013, vol. 54, num. 9, p. 2475-2484
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ISSN: 0022-2275
Appears in Collections:Articles publicats en revistes (Bioquímica i Biomedicina Molecular)

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