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SLC5A7  -  solute carrier family 5 (sodium/choline...

Homo sapiens

Synonyms: CHT, CHT1, HMN7A, Hemicholinium-3-sensitive choline transporter, High affinity choline transporter 1, ...
 
 
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Disease relevance of SLC5A7

  • A better understanding of modes of CHT regulation should allow for experimental manipulation of cholinergic signaling in vivo with potential utility in human disorders of known cholinergic dysfunction such as Alzheimer's disease, Parkinson's disease, schizophrenia, Huntington's disease, and dysautonomia [1].
  • CONCLUSIONS: Data from observational studies support the association of increased but considerably different risks for breast cancer incidence among current users of ET and CHT [2].
  • Toxicity and ease of administration compare favorably with those reported for CHT regimens used in this setting [3].
  • Patients and Methods: Between 1991 and 2003, 210 patients with locally advanced rectal cancer (65 International Union Against Cancer [UICC] Stage II, 116 UICC Stage III, and 29 UICC Stage IV cancers) were treated with TME, IOERT, and preoperative or postoperative CHT [4].
  • Human recombinant granulocyte-macrophage colony-stimulating-factor has been employed, on a compassionate basis, in 14 hematological patients in order to reduce the duration of the neutropenic period after high-dose chemotherapy for the treatment of hematological malignancies (7 traditional CHT courses, 7 autologous bone marrow transplantations) [5].
 

Psychiatry related information on SLC5A7

 

High impact information on SLC5A7

 

Chemical compound and disease context of SLC5A7

 

Biological context of SLC5A7

 

Anatomical context of SLC5A7

  • In contrast, overexpression of VAChT or CHT1 with SEC14L1 recruited the latter to large intracellular organelles similar to vesicles or vesicle aggregates [16].
  • Expression of hCHT cDNA in COS-7 cells results in saturable, Na(+)/Cl(-)-dependent choline uptake (K(m) = 1.2 microM) in membrane vesicles and [(3)H] HC-3 binding (K(d) = 4 nM) in membrane fractions, consistent with characteristics reported in mammalian cholinergic neurons [14].
  • Subcellular fractionation and immunoisolation of organelles from rat brain indicate that CHT1 is present in synaptic vesicles [17].
  • In a neuronal cell line, CHT1-HA colocalizes with the early endocytic marker green fluorescent protein (GFP)-Rab 5 and with two markers of synaptic-like vesicles, VAMP-myc and GFP-VAChT, suggesting that in cultured cells CHT1 is present mainly in organelles of endocytic origin [17].
  • Binding of [3H]hemicholinium-3 to the high-affinity choline transporter in electric organ synaptosomal membranes [15].
 

Associations of SLC5A7 with chemical compounds

  • The hCHT1 exhibits significant homology with known members of the Na(+)-dependent glucose transporter family, but not with members of the neurotransmitter transporter family [13].
  • In cholinergic neurons, the presynaptic choline transporter (CHT) mediates high-affinity choline uptake (HACU) as the rate-limiting step in acetylcholine (ACh) synthesis [1].
  • Maintenance of acetylcholine (ACh) synthesis depends on the activity of the high-affinity choline transporter (CHT1), which is responsible for the reuptake of choline from the synaptic cleft into presynaptic neurons [11].
  • RESULTS: Control experiments established that the antibody to human CHT selectively labeled cholinergic neurons in the guinea pig [18].
  • On the basis of these data, the next 8 patients (Group 3) received three cycles of neoadjuvant TPF followed by two cycles only of CHT (cisplatin 20 mg/m(2) on Days 1-4 and 5-fluorouracil 800 mg/m(2)/d continuous infusion for 96 h) (PF) during Weeks 1 and 6 of the planned 7 weeks of RT [19].
 

Analytical, diagnostic and therapeutic context of SLC5A7

References

  1. The high-affinity choline transporter: a critical protein for sustaining cholinergic signaling as revealed in studies of genetically altered mice. Bazalakova, M.H., Blakely, R.D. Handbook of experimental pharmacology. (2006) [Pubmed]
  2. Postmenopausal hormone therapy and breast cancer: a systematic review and meta-analysis. Shah, N.R., Borenstein, J., Dubois, R.W. Menopause (New York, N.Y.) (2005) [Pubmed]
  3. Low-dose continuous oral fosfestrol is highly active in 'hormone-refractory' prostate cancer. Orlando, M., Chacón, M., Salum, G., Chacón, D.R. Ann. Oncol. (2000) [Pubmed]
  4. Long-term results of intraoperative presacral electron boost radiotherapy (IOERT) in combination with total mesorectal excision (TME) and chemoradiation in patients with locally advanced rectal cancer. Krempien, R., Roeder, F., Oertel, S., Roebel, M., Weitz, J., Hensley, F.W., Timke, C., Funk, A., Bischof, M., Zabel-Du Bois, A., Niethammer, A.G., Eble, M.J., Buchler, M.W., Treiber, M., Debus, J. Int. J. Radiat. Oncol. Biol. Phys. (2006) [Pubmed]
  5. Accelerated hemopoietic recovery after chemotherapy and autologous bone marrow transplantation in hematological malignancies using recombinant GM-CSF: preliminary results obtained in 14 cases. Visani, G., Tosi, P., Gamberi, B., Cenacchi, A., Mazzanti, P., Stabilini, C., Bandini, G., Mazza, P., Gherlinzoni, F., Cavo, M. Haematologica (1990) [Pubmed]
  6. Overexpression of the high affinity choline transporter in cortical regions affected by Alzheimer's disease. Evidence from rapid autopsy studies. Slotkin, T.A., Nemeroff, C.B., Bissette, G., Seidler, F.J. J. Clin. Invest. (1994) [Pubmed]
  7. Reduction in CHT1-mediated choline uptake in primary neurons from presenilin-1 M146V mutant knock-in mice. Payette, D.J., Xie, J., Guo, Q. Brain Res. (2007) [Pubmed]
  8. Par-4 inhibits choline uptake by interacting with CHT1 and reducing its incorporation on the plasma membrane. Xie, J., Guo, Q. J. Biol. Chem. (2004) [Pubmed]
  9. Single nucleotide polymorphism of the human high affinity choline transporter alters transport rate. Okuda, T., Okamura, M., Kaitsuka, C., Haga, T., Gurwitz, D. J. Biol. Chem. (2002) [Pubmed]
  10. Cortical choline transporter function measured in vivo using choline-sensitive microelectrodes: clearance of endogenous and exogenous choline and effects of removal of cholinergic terminals. Parikh, V., Sarter, M. J. Neurochem. (2006) [Pubmed]
  11. The "ins" and "outs" of the high-affinity choline transporter CHT1. Ribeiro, F.M., Black, S.A., Prado, V.F., Rylett, R.J., Ferguson, S.S., Prado, M.A. J. Neurochem. (2006) [Pubmed]
  12. Changes of thymidine kinase (TK) during adjuvant and palliative chemotherapy. Topolcan, O., Holubec, L., Finek, J., Stieber, P., Holdenrieder, S., Lamerz, R., Holubec Sen, L., Svobodova, S., Visokai, V., Lipska, L. Anticancer Res. (2005) [Pubmed]
  13. Functional characterization of the human high-affinity choline transporter. Okuda, T., Haga, T. FEBS Lett. (2000) [Pubmed]
  14. Molecular cloning of a human, hemicholinium-3-sensitive choline transporter. Apparsundaram, S., Ferguson, S.M., George, A.L., Blakely, R.D. Biochem. Biophys. Res. Commun. (2000) [Pubmed]
  15. Binding of [3H]hemicholinium-3 to the high-affinity choline transporter in electric organ synaptosomal membranes. O'Regan, S. J. Neurochem. (1988) [Pubmed]
  16. SEC14-like protein 1 interacts with cholinergic transporters. Ribeiro, F.M., Ferreira, L.T., Marion, S., Fontes, S., Gomez, M., Ferguson, S.S., Prado, M.A., Prado, V.F. Neurochem. Int. (2007) [Pubmed]
  17. The hemicholinium-3 sensitive high affinity choline transporter is internalized by clathrin-mediated endocytosis and is present in endosomes and synaptic vesicles. Ribeiro, F.M., Alves-Silva, J., Volknandt, W., Martins-Silva, C., Mahmud, H., Wilhelm, A., Gomez, M.V., Rylett, R.J., Ferguson, S.S., Prado, V.F., Prado, M.A. J. Neurochem. (2003) [Pubmed]
  18. Localization of cholinergic innervation in guinea pig heart by immunohistochemistry for high-affinity choline transporters. Hoover, D.B., Ganote, C.E., Ferguson, S.M., Blakely, R.D., Parsons, R.L. Cardiovasc. Res. (2004) [Pubmed]
  19. Neoadjuvant docetaxel, cisplatin, 5-fluorouracil before concurrent chemoradiotherapy in locally advanced squamous cell carcinoma of the head and neck versus concomitant chemoradiotherapy: a phase II feasibility study. Ghi, M.G., Paccagnella, A., D'Amanzo, P., Mione, C.A., Fasan, S., Paro, S., Mastromauro, C., Carnuccio, R., Turcato, G., Gatti, C., Pallini, A., Nascimben, O., Biason, R., Oniga, F., Medici, M., Rossi, F., Fila, G. Int. J. Radiat. Oncol. Biol. Phys. (2004) [Pubmed]
  20. Management of primary anal canal adenocarcinoma: a large retrospective study from the Rare Cancer Network. Belkacémi, Y., Berger, C., Poortmans, P., Piel, G., Zouhair, A., Méric, J.B., Nguyen, T.D., Krengli, M., Behrensmeier, F., Allal, A., De Looze, D., Bernier, J., Scandolaro, L., Mirimanoff, R.O. Int. J. Radiat. Oncol. Biol. Phys. (2003) [Pubmed]
 
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