Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2010-5-13
pubmed:abstractText
Ascorbate (vitamin C) is the major electron donor to a tPMET (transplasma membrane electron transport) system that was originally identified in human erythrocytes. This plasma membrane redox system appears to transfer electrons from intracellular ascorbate to extracellular oxidants (e.g. non-transferrin-bound iron). Although this phenomenon has been observed in nucleated cells, its mechanism and regulation are not well understood. In the present study we have examined both facets of this phenomenon in K562 cells and primary astrocyte cultures. Using ferricyanide as the analytical oxidant we demonstrate that tPMET is enhanced by dehydroascorbate uptake via facilitative glucose transporters, and subsequent accumulation of intracellular ascorbate. Additionally, we demonstrate that this stimulation is not due to ascorbate that is released from the cells, but is dependent only on a restricted intracellular pool of the vitamin. Substrate-saturation kinetics suggest an enzyme-catalysed reaction across the plasma membrane by an as-yet-unidentified reductase that relies on extensive recycling of intracellular ascorbate. Inhibition of ascorbate-stimulated tPMET by the NHE (Na(+)/H(+)-exchanger) inhibitors amiloride and 5-(N-ethyl-N-isopropyl)amiloride, which is diminished by bicarbonate, suggests that tPMET activity may be regulated by intracellular pH. In support of this hypothesis, tPMET in astrocytes was significantly inhibited by ammonium chloride-pulse-induced intracellular acidification, whereas it was significantly stimulated by bicarbonate-induced intracellular alkalinization. These results suggest that ascorbate-dependent tPMET is enzyme-catalysed and is modulated by NHE activity and intracellular pH.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1470-8728
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
428
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
191-200
pubmed:dateRevised
2010-9-22
pubmed:meshHeading
pubmed-meshheading:20307259-Amiloride, pubmed-meshheading:20307259-Animals, pubmed-meshheading:20307259-Animals, Newborn, pubmed-meshheading:20307259-Ascorbic Acid, pubmed-meshheading:20307259-Astrocytes, pubmed-meshheading:20307259-Cell Line, Tumor, pubmed-meshheading:20307259-Cell Membrane, pubmed-meshheading:20307259-Cells, Cultured, pubmed-meshheading:20307259-Dehydroascorbic Acid, pubmed-meshheading:20307259-Electron Transport, pubmed-meshheading:20307259-Ferricyanides, pubmed-meshheading:20307259-Fluorometry, pubmed-meshheading:20307259-Humans, pubmed-meshheading:20307259-Hydrogen-Ion Concentration, pubmed-meshheading:20307259-Mice, pubmed-meshheading:20307259-Mice, Inbred C57BL, pubmed-meshheading:20307259-Oxidation-Reduction, pubmed-meshheading:20307259-Rats, pubmed-meshheading:20307259-Rats, Wistar, pubmed-meshheading:20307259-Sodium-Hydrogen Antiporter
pubmed:year
2010
pubmed:articleTitle
A role for Na+/H+ exchangers and intracellular pH in regulating vitamin C-driven electron transport across the plasma membrane.
pubmed:affiliation
Department of Biochemistry and Molecular Biology, Monash University, VIC 3800, Australia.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't