+ Resolve Article
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter

+ Translate
+ Subscribe to Site Feed
GeoScience Most Shared ContentMost Shared Content

The human tumour suppressor gene SLC5A8 expresses a Na+-monocarboxylate cotransporter

, : The human tumour suppressor gene SLC5A8 expresses a Na+-monocarboxylate cotransporter. Journal of Physiology 557(Pt 3): 719-731

The orphan cotransport protein expressed by the SLC5A8 gene has been shown to play a role in controlling the growth of colon cancers, and the silencing of this gene is a common and early event in human colon neoplasia. We expressed this protein in Xenopus laevis oocytes and have found that it transports small monocarboxylic acids. The electrogenic activity of the cotransporter, which we have named SMCT (sodium monocarboxylate transporter), was dependent on external Na(+) and was compatible with a 3 : 1 stoichiometry between Na(+) and monocarboxylates. A portion of the SMCT-mediated current was also Cl(-) dependent, but Cl(-) was not cotransported. SMCT transports a variety of monocarboxylates (similar to unrelated monocarboxylate transport proteins) and most transported monocarboxylates demonstrated K(m) values near 100 microm, apart from acetate and d-lactate, for which the protein showed less affinity. SMCT was strongly inhibited by 1 mm probenecid or ibuprofen. In the absence of external substrate, a Na(+)-independent leak current was also observed to pass through SMCT. SMCT activity was strongly inhibited after prolonged exposure to high external concentrations of monocarboxylates. The transport of monocarboxylates in anionic form was confirmed by the observation of a concomitant alkalinization of the cytosol. SMCT, being expressed in colon and kidney, represents a novel means by which Na(+), short-chain fatty acids and other monocarboxylates are transported in these tissues. The significance of a Na(+)-monocarboxylate transporter to colon cancer presumably stems from the transport of butyrate, which is well known for having anti-proliferative and apoptosis-inducing activity in colon epithelial cells.


PMID: 15090606

DOI: 10.1113/jphysiol.2004.063859

Other references

Zhonglian Yang; Baoyu Gao; Yan Wang; Yaqin Zhao; Qinyan Yue, 2012: Fractionation of residual Al in natural water treatment from reservoir with poly-aluminum-silicate-chloride PASiC Effect of OH/Al, Si/Al molar ratios and initial pH. An aluminum fractionation study was conducted for a surface reservoir water treatment to understand the performance of poly-aluminum-silicate-chloride (PASiC) in terms of the residual Al fractions as a function of initial pH. The coagulation perfo...

Choi M.J.; Fernandez P.C.; Patnaik A.; Coupaye Gerard B.; D'andrea D.; Szerlip H.; Kleyman T.R., 1992: Hyperkalemia and renal salt wasting due to the potassium sparing diuretic effects of trimethoprim. Journal of the American Society of Nephrology 3(3): 325

Kovalenko, F.P.; Dzhabarova, V.I.; Rudakov, V.A.; Krotov, A.I.; Shadrin, B.P., 1986: Methods of reproducing a model of larval multilocular echinococcosis with a primary lesion of the liver or the lungs. Meditsinskaia Parazitologiia i Parazitarnye Bolezni: 71-74

Cooke, D.T.; Zheng, D.J.; Peterson, K.A.; Calhoun, R.F., 2010: Synchronous pulmonary renal cell carcinoma metastases and primary non-small cell lung cancer. Journal of Thoracic Oncology 5(1): 140-141

Van Der Want J.J.L., 1987: Anterograde tracing of neuronal pathways using transport of wga hrp and pha l at the light microscopic and electron microscopical levels. Neuroscienceppl: S9

Ishida, Y.; Kawada, T.; Sugino, N., 1983: Urinary enzyme determination and its clinical significance. C. Enzyme derived from the kidney tubular epithelium--N-acetyl-beta-D-glucosaminidase. 11. Clinical significance of urinary NAG activity in patients with kidney diseases and those with kidney homografts. Rinsho Byori. Japanese Journal of Clinical Pathology Spec No 56: 160-167

Lüst, R., 1965: The European Space Research Organization. The European Space Research Organization [ESRO], which was established in 1964 for the purpose of promoting collaboration in space research among European nations, has made plans for its initial program. The projects already agreed upon include th...

Moradpour, D.; Blum, H.E., 1996: Hepatitis C, diagnosis and therapy. Medizinische Klinik 91(12): 769-770

Yamaguchi, R.; Sato, M.; Tsuchiya, H.; Yamamoto, K.; Doi, Y.; Iwaku, F., 1996: A method for evaluating the cariogenicity of oral bacteria using radio-labelled synthetic hydroxyapatite. Radioactive hydroxyapatite was synthesized using 45Ca to evaluate the cariogenicity of oral streptococci. Discs prepared from it were suspended in media containing sucrose, then inoculated with Streptococcus mutans or Streptococcus sanguis. The ra...

Shima F.; Futagawa S., 1975: Ultrasonic examination of breast tumor. Ultrasound in Medicine & Biology 1(4): 456