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NCBI
Solute carrier family 5 (Iodide transporter), Member 8; SLC5A8
NCBI (National Center for Biotechnology Information)
Apical Iodide Transporter -- AIT
Sodium-coupled Monocarboxylate Transporter -- SMCT
"By analyzing iodide transport in transfected COS-7 and Chinese hamster ovary cells, Rodriguez et al. (2002) determined that AIT catalyzes passive iodide transport.
"By functional analysis using Xenopus oocytes, Li et al. (2003) showed that SLC5A8 encodes a sodium transporter.
"Li et al. (2003) identified SLC5A8 as a candidate tumor suppressor gene whose silencing by aberrant methylation is a common and early event in human colon neoplasia. They found that, in normal colon mucosa, SLC5A8 exon 1 was unmethylated and SLC5A8 transcript was expressed. In contrast, SLC5A8 exon 1 was aberrantly methylated in 59% of primary colon cancers and 52% of colon cancer cell lines tested. Cells in which SLC5A8 exon 1 was methylated were uniformly silenced for SLC5A8 expression, but reactivated expression was achieved by treatment with a demethylating drug, 5-azacytidine. Transfection of SLC5A8 suppressed colony growth in each of 3 SLC5A8-deficient cell lines, but showed no suppressive effect in any of 3 SLC5A8-proficient cell lines. Li et al. (2003) suggested that SLC5A8 methylation might be a high-quality marker of colon cancer presence. Because aberrantly methylated genomic DNA from specific loci can be detected in the serum of some cancer patients, they characterized the level of SLC5A8 methylation in ethanol-precipitable DNA prepared from the serum of colon cancer patients. SLC5A8 methylation was totally undetectable in DNA extracted from each of 13 serum samples from individuals with colon cancers in which SLC5A8 assayed as unmethylated. In contrast, SLC5A8 methylation was detectable in serum DNA from 4 of 10 patients in whom the underlying colon cancer assayed as SLC5A8-methylated.
Following expression in mammalian cells and Xenopus oocytes, Gopal et al. (2004) demonstrated that mouse Slc5a8 mediated Na(+)-coupled electrogenic transport of lactate, pyruvate, and short-chain fatty acids, such as acetate, propionate, and butyrate. The Na(+)/fatty acid stoichiometry varied depending on the fatty acid substrate (2:1 for lactate and 4:1 for propionate). The phenomenon of variable Na(+)/substrate stoichiometry was also found with human SLC5A8. In situ hybridization of sagittal sections of mouse kidney demonstrated abundant expression of Slc5a8 in both the cortex and medulla. Brush border membrane vesicles prepared from rabbit kidney were able to transport lactate in a Na(+)-coupled manner. The transport process exhibited the overshoot phenomenon, indicating uphill lactate transport in response to the transmembrane Na(+) gradient. The Na(+)-coupled lactate transport in these membrane vesicles could be inhibited by short-chain fatty acids. Gopal et al. (2004) concluded that SLC5A8 plays a role in the active renal reabsorption of lactate.
Porra et al. (2005) examined the expression pattern of SLC5A8 in normal human thyrocytes and in 50 hypofunctioning tumors. SLC5A8 expression was studied at the transcript level and compared with that of SLC26A4 (605646) and SLC5A5. SLC5A8 expression, unlike that of SLC5A5 and SLC26A4, was not regulated by TSH (see 188540) in normal human thyrocytes in culture and was not related to the functional state of thyroid tissue; toxic adenomas and adjacent resting tissues exhibited the same SLC5A8 transcript content. SLC5A8 expression was selectively downregulated (40-fold) in papillary thyroid carcinomas (PTCs; 188550) of classical form. Methylation-specific PCR analyses showed that SLC5A8 was methylated in 90% of classical PTCs and in about 20% of other PTCs. In a series of 52 classical PTCs, a low SLC5A8 expression was highly significantly associated with the presence of the BRAF T1796A mutation (164757.0001). Porra et al. (2005) concluded that their data identified a relationship between the methylation-associated silencing of the tumor-suppressor gene SLC5A8 and the T1796A point mutation of the BRAF gene in the classical PTC subtype of thyroid carcinomas."