Constitutive activation of nuclear factor‐E2‐related factor 2 induces biotransformation enzyme and transporter expression in livers of mice with hepatocyte‐specific deletion ofKelch‐like ECH‐associated protein 1
Copyright policy )Constitutive activation of nuclear factor‐E2‐related factor 2 induces biotransformation enzyme and transporter expression in livers of mice with hepatocyte‐specific deletion ofKelch‐like ECH‐associated protein 1
AbstractChemicals that activate nuclear factor‐E2‐related factor 2 (Nrf2) often increase multidrug‐resistance‐associated protein (Mrp) expression in liver. Hepatocyte‐specific deletion of Kelch‐like ECH‐associated protein 1 (Keap1) activates Nrf2. Use of hepatocyte‐specificKeap1deletion represents a nonpharmacological method to determine whether constitutive Nrf2 activation upregulates liver transporter expression in vivo. The mRNA, protein expression, and localization of several biotransformation and transporters were determined in livers of wild‐type and hepatocyte‐specificKeap1‐null mice. Sulfotransferase 2a1/2, NADP(H):quinone oxidoreductase 1, cytochrome P450 2b10, 3a11, and glutamate–cysteine ligase catalytic subunit expression were increased in livers ofKeap1‐null mice. Organic anion‐transporting polypeptide 1a1 expression was nearly abolished, as compared to that detected in livers of wild‐type mice. By contrast, Mrp 1–5 mRNA and protein levels were increased inKeap1‐null mouse livers, with Mrp4 expression being more than 15‐fold higher than wild types. In summary, Nrf2 has a significant role in affecting Oatp and Mrp expressions. © 2011 Wiley Periodicals, Inc. J Biochem Mol Toxicol 25:320–329, 2011; View this article online atwileyonlinelibrary.com. DOI 10.1002/jbt.20392
- University of Arizona United States
- University of Rhode Island United States
- University of Connecticut United States
- Tohoku University Japan
Mice, Knockout, 570, Kelch-Like ECH-Associated Protein 1, NF-E2-Related Factor 2, Glutamate-Cysteine Ligase, 610, Organic Anion Transporters, Drug Resistance, Multiple, Cytoskeletal Proteins, Mice, Cytochrome P-450 Enzyme System, Gene Expression Regulation, Liver, Hepatocytes, NAD(P)H Dehydrogenase (Quinone), Animals, Multidrug Resistance-Associated Proteins, Gene Deletion, Adaptor Proteins, Signal Transducing, Signal Transduction
Mice, Knockout, 570, Kelch-Like ECH-Associated Protein 1, NF-E2-Related Factor 2, Glutamate-Cysteine Ligase, 610, Organic Anion Transporters, Drug Resistance, Multiple, Cytoskeletal Proteins, Mice, Cytochrome P-450 Enzyme System, Gene Expression Regulation, Liver, Hepatocytes, NAD(P)H Dehydrogenase (Quinone), Animals, Multidrug Resistance-Associated Proteins, Gene Deletion, Adaptor Proteins, Signal Transducing, Signal Transduction
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