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Past-A, a novel proton-associated sugar transporter, regulates glucose homeostasis in the brain.
Ludwiginstitutet för Cancerforskning.
Ludwiginstitutet för Cancerforskning.
Ludwiginstitutet för Cancerforskning.
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2002 (English)In: J Neurosci, ISSN 1529-2401, Vol. 22, no 21, 9160-5 p.Article in journal (Refereed) Published
Abstract [en]

The ventral medullary surface (VMS) of the medulla oblongata is known to be the site of the central chemosensitive neurons in mammals. These neurons sense excess H+/CO2 dissolved in the CSF and induce hyperventilation. To elucidate the mechanism of neuronal cell adaptation to changes of H+/CO2, we screened for hypercapnia-induced genes in the VMS. Here, we report cloning and characterization of a novel gene called proton-associated sugar transporter-A (Past-A), which is induced in the brain after hypercapnia and mediates glucose uptake along the pH gradient. Past-A comprises 751 amino acid residues containing 12 membrane-spanning helices, several conserved sugar transport motifs, three proline-rich regions, and leucine repeats. Past-A transcript was expressed predominantly in the brain. Moreover, the Past-A-immunoreactive neural cells were found in the VMS of the medulla oblongata, and the number of immunoreactive cells was increased by hypercapnic stimulation. Transient transfection of Past-A in COS-7 cells leads to the expression of a membrane-associated 82 kDa protein that possesses a glucose transport activity. The acidification of extracellular medium facilitated glucose uptake, whereas the addition of carbonyl cyanide m-chlorophenylhydrazone, a protonophore, inhibited glucose import. Together, our results indicate that Past-A is a brain-specific glucose transporter that may represent an adaptation mechanism regulating sugar homeostasis in neuronal cells after hypercapnia.

Place, publisher, year, edition, pages
2002. Vol. 22, no 21, 9160-5 p.
Keyword [en]
Administration; Inhalation, Amino Acid Sequence, Animals, Biological Transport/physiology, Blotting; Northern, Brain/cytology/drug effects/*metabolism, COS Cells/metabolism, Carbon Dioxide/administration & dosage, Carrier Proteins/genetics/*metabolism, Chemoreceptors/drug effects/metabolism, Gene Expression Profiling, Glucose/*metabolism/pharmacokinetics, Homeostasis/*physiology, Hydrogen-Ion Concentration, Hypercapnia/chemically induced/*metabolism, Immunohistochemistry, Male, Medulla Oblongata/cytology/drug effects/metabolism, Molecular Sequence Data, Monosaccharide Transport Proteins/genetics/*metabolism, Neurons/drug effects/metabolism, Organ Specificity, Phylogeny, Pons/cytology/drug effects/metabolism, RNA; Messenger/metabolism, Rats, Rats; Wistar
Identifiers
URN: urn:nbn:se:uu:diva-10461PubMedID: 12417639OAI: oai:DiVA.org:uu-10461DiVA: diva2:38229
Available from: 2007-03-26 Created: 2007-03-26 Last updated: 2011-01-13

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