Sodium-coupled monocarboxylate transporters in normal tissues and in cancer.
dc.contributor.author | Ganapathy, Vadivel | |
dc.contributor.author | Thangaraju, Muthusamy | |
dc.contributor.author | Gopal, Elangovan | |
dc.contributor.author | Martin, Pamela M | |
dc.contributor.author | Itagaki, Shiro | |
dc.contributor.author | Miyauchi, Seiji | |
dc.contributor.author | Prasad, Puttur D | |
dc.date.accessioned | 2010-09-24T22:03:25Z | |
dc.date.available | 2010-09-24T22:03:25Z | |
dc.date.issued | 2008-04-30 | en_US |
dc.identifier.citation | AAPS J. 2008 Apr 2; 10(1):193-199 | en_US |
dc.identifier.issn | 1550-7416 | en_US |
dc.identifier.pmid | 18446519 | en_US |
dc.identifier.doi | 10.1208/s12248-008-9022-y | en_US |
dc.identifier.uri | http://hdl.handle.net/10675.2/133 | |
dc.description.abstract | SLC5A8 and SLC5A12 are sodium-coupled monocarboxylate transporters (SMCTs), the former being a high-affinity type and the latter a low-affinity type. Both transport a variety of monocarboxylates in a Na(+)-coupled manner. They are expressed in the gastrointestinal tract, kidney, thyroid, brain, and retina. SLC5A8 is localized to the apical membrane of epithelial cells lining the intestinal tract and proximal tubule. In the brain and retina, its expression is restricted to neurons and the retinal pigment epithelium. The physiologic functions of SLC5A8 include absorption of short-chain fatty acids in the colon and small intestine, reabsorption of lactate and pyruvate in the kidney, and cellular uptake of lactate and ketone bodies in neurons. It also transports the B-complex vitamin nicotinate. SLC5A12 is also localized to the apical membrane of epithelial cells lining the intestinal tract and proximal tubule. In the brain and retina, its expression is restricted to astrocytes and M?�ller cells. SLC5A8 also functions as a tumor suppressor; its expression is silenced in tumors of colon, thyroid, stomach, kidney, and brain. The tumor-suppressive function is related to its ability to mediate concentrative uptake of butyrate, propionate, and pyruvate, all of which are inhibitors of histone deacetylases. SLC5A8 can also transport a variety of pharmacologically relevant monocarboxylates, including salicylates, benzoate, and gamma-hydroxybutyrate. Non-steroidal anti-inflammatory drugs such as ibuprofen, ketoprofen, and fenoprofen, also interact with SLC5A8. These drugs are not transportable substrates for SLC5A8, but instead function as blockers of the transporter. Relatively less is known on the role of SLC5A12 in drug transport. | |
dc.rights | The PMC Open Access Subset is a relatively small part of the total collection of articles in PMC. Articles in the PMC Open Access Subset are still protected by copyright, but are made available under a Creative Commons or similar license that generally allows more liberal redistribution and reuse than a traditional copyrighted work. Please refer to the license statement in each article for specific terms of use. The license terms are not identical for all articles in this subset. | en_US |
dc.subject.mesh | Animals | en_US |
dc.subject.mesh | Humans | en_US |
dc.subject.mesh | Monocarboxylic Acid Transporters / metabolism | en_US |
dc.subject.mesh | Neoplasms / metabolism | en_US |
dc.subject.mesh | Sodium / metabolism | en_US |
dc.subject.mesh | Sodium Channels / metabolism | en_US |
dc.subject.mesh | Sodium-Glucose Transport Proteins / metabolism | en_US |
dc.subject.mesh | Tissue Distribution | en_US |
dc.title | Sodium-coupled monocarboxylate transporters in normal tissues and in cancer. | en_US |
dc.type | Comparative Study | en_US |
dc.type | Journal Article | en_US |
dc.type | Review | en_US |
dc.identifier.pmcid | PMC2751467 | en_US |
dc.contributor.corporatename | Department of Biochemistry and Molecular Biology | en_US |
refterms.dateFOA | 2019-04-09T16:25:55Z | |
html.description.abstract | SLC5A8 and SLC5A12 are sodium-coupled monocarboxylate transporters (SMCTs), the former being a high-affinity type and the latter a low-affinity type. Both transport a variety of monocarboxylates in a Na(+)-coupled manner. They are expressed in the gastrointestinal tract, kidney, thyroid, brain, and retina. SLC5A8 is localized to the apical membrane of epithelial cells lining the intestinal tract and proximal tubule. In the brain and retina, its expression is restricted to neurons and the retinal pigment epithelium. The physiologic functions of SLC5A8 include absorption of short-chain fatty acids in the colon and small intestine, reabsorption of lactate and pyruvate in the kidney, and cellular uptake of lactate and ketone bodies in neurons. It also transports the B-complex vitamin nicotinate. SLC5A12 is also localized to the apical membrane of epithelial cells lining the intestinal tract and proximal tubule. In the brain and retina, its expression is restricted to astrocytes and M?�ller cells. SLC5A8 also functions as a tumor suppressor; its expression is silenced in tumors of colon, thyroid, stomach, kidney, and brain. The tumor-suppressive function is related to its ability to mediate concentrative uptake of butyrate, propionate, and pyruvate, all of which are inhibitors of histone deacetylases. SLC5A8 can also transport a variety of pharmacologically relevant monocarboxylates, including salicylates, benzoate, and gamma-hydroxybutyrate. Non-steroidal anti-inflammatory drugs such as ibuprofen, ketoprofen, and fenoprofen, also interact with SLC5A8. These drugs are not transportable substrates for SLC5A8, but instead function as blockers of the transporter. Relatively less is known on the role of SLC5A12 in drug transport. |