Compensatory Expression of MRP3 in the Livers of MRP2-Deficient EHBRs Is Promoted by DHA Intake
| Autor: | Seiji Sekine, Kazuhiro Kubo, Morio Saito |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Male
medicine.medical_specialty Docosahexaenoic Acids Organic anion transporter 1 alpha-Tocopherol Biology Thiobarbituric Acid Reactive Substances Applied Microbiology and Biotechnology Biochemistry Analytical Chemistry Rats Sprague-Dawley Excretion Lipid peroxidation Eating chemistry.chemical_compound Malondialdehyde Internal medicine medicine Animals RNA Messenger Mercapturic acid Molecular Biology Multidrug resistance-associated protein 2 Body Weight Organic Chemistry Bilirubin Hydrogen Peroxide Organ Size General Medicine Glutathione Dietary Fats Multidrug Resistance-Associated Protein 2 Acetylcysteine Rats Endocrinology Gene Expression Regulation Liver chemistry Docosahexaenoic acid biology.protein Lipid Peroxidation Multidrug Resistance-Associated Proteins Biotechnology |
| Zdroj: | Bioscience, Biotechnology, and Biochemistry. 73:2432-2438 |
| ISSN: | 1347-6947 0916-8451 |
| DOI: | 10.1271/bbb.90387 |
| Popis: | We have hypothesized a suppressive mechanism against dietary docosahexaenoic acid (22:6n-3; DHA)-induced tissue lipid peroxidation, in which the degradation products, including their conjugates, are excreted into the urine by xenobiotic or organic anion transporters. In this study, we employed parent-strain Sprague-Dawley rats (SDRs), together with their mutant strain, Eisai hyperbilirubinuria rats (EHBRs). EHBRs are deficient in multidrug resistance-associated protein (MRP) 2, and show defective urinary excretion of numerous xenobiotics and organic anions. Both strains of rats were fed a diet containing DHA at 8.4% of total energy for 31 d. In the livers of the DHA-fed rats, the level of free malondialdehyde (MDA) + 4-hydroxy-2-alkenals (HAE) fell, and conversely glutathione S-transferase (GST) activity increased in MRP2-deficient EHBRs as compared to the SDRs, suggesting that the glutathione (GSH)-conjugation reaction for the aldehydes generated on DHA intake was accelerated in the MRP2-deficient EHBRs. Since the gene expression of liver MRP3 in the MRP2-deficient EHBRs was amplified to compensate for DHA intake, it is thought that the transport of MRP3 substrates into the bloodstream, rather than MRP2-mediated excretion of its substrates into the bile, was promoted. Indeed, excretion of mercapturic acid (acetylcysteine conjugates derived metabolically from the conjugate of each aldehyde with GSH) into the urine increased significantly in MRP2-deficient EHBRs fed DHA. |
| Databáze: | OpenAIRE |
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