Expression of slc5a8 in Kidney and Its Role in Na+-coupled Transport of Lactate
| Autor: | Elangovan Gopal, Lina Zhuang, Puttur D. Prasad, Mitsuru Sugawara, You Jun Fei, Pamela M. Martin, Sylvia B. Smith, Vadivel Ganapathy, Seiji Miyauchi |
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| Rok vydání: | 2004 |
| Předmět: |
Monocarboxylic Acid Transporters
Lactate transport DNA Complementary Time Factors Coumaric Acids Brush border Xenopus Molecular Sequence Data Butyrate Biology Kidney Transfection Models Biological Biochemistry RNA Complementary Substrate Specificity Mice Xenopus laevis Animals Humans Tissue Distribution Cloning Molecular Intestinal Mucosa Pyruvates Cation Transport Proteins Molecular Biology In Situ Hybridization chemistry.chemical_classification Dose-Response Relationship Drug Microvilli Reabsorption Fatty Acids Sodium Fatty acid Kidney metabolism Biological Transport Cell Biology Hydrogen-Ion Concentration Blotting Northern Amino acid Kinetics chemistry Lactates Oocytes Propionate Rabbits Propionates |
| Zdroj: | Journal of Biological Chemistry. 279:44522-44532 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m405365200 |
| Popis: | We report here on the expression of slc5a8 in kidney and its relevance to Na(+)-coupled reabsorption of lactate. slc5a8 is the murine ortholog of SLC5A8, a candidate tumor suppressor gene, which we recently cloned from human intestine and demonstrated its functional identity as a Na(+)-coupled transporter for short-chain fatty acids and lactate. The slc5a8 cDNA, cloned from mouse kidney, codes for a protein consisting of 611 amino acids. When expressed heterologously in mammalian cells or Xenopus oocytes, slc5a8 mediates Na(+)-coupled electrogenic transport of lactate/pyruvate as well as short-chain fatty acids (e.g. acetate, propionate, and butyrate). The Na+/fatty acid stoichiometry varies depending on the fatty acid substrate (2:1 for lactate and 4:1 for propionate). This phenomenon of variable Na+/substrate stoichiometry depending on the fatty acid substrate is also demonstrable with human SLC5A8. In situ hybridization with sagittal sections of mouse kidney demonstrates abundant expression of the transcripts in the cortex as well as the medulla. Brush border membrane vesicles prepared from rabbit kidney are able to transport lactate in a Na(+)-coupled manner. The transport process exhibits the overshoot phenomenon, indicating uphill lactate transport in response to the transmembrane Na+ gradient. The Na(+)-coupled lactate transport in these membrane vesicles is inhibitable by short-chain fatty acids. We conclude that slc5a8 is expressed abundantly in the kidney and that it plays a role in the active reabsorption of lactate. slc5a8 is the first transporter known to be expressed in mammalian kidney that has the ability to mediate the Na(+)-coupled reabsorption of lactate. |
| Databáze: | OpenAIRE |
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