Interactions among ascorbate, dehydroascorbate and glucose transport in cultured hippocampal neurons and glia.
There is an increasing recognition of the damaging role played by oxygen radicals in mediating necrotic neuronal injury. As such, it becomes important to understand the transport mechanisms that help maintain appropriate levels of small molecule antioxidants such as ascorbate in the brain. It has long been known that the transport of dehydroascorbate (DHA) into a variety of cell types is accomplished through the Glut-1 glucose transporter. In this paper, we characterize interactions among the transports of ascorbate, DHA and glucose in hippocampal cultures. We find: (a) sodium-dependent transport of ascorbate in mixed neuronal/glial, pure glial, and neuron-enriched hippocampal cultures; in contrast, we observed no such transport of DHA; (b) such ascorbate transport appeared to be independent of the glucose transporter, in that glucose did not compete for such transport, and overexpression of the Glut-1 glucose transporter did not alter ascorbate uptake; (c) in contrast, ascorbate, at concentrations ranging from 1 to 20 mM inhibited 2-dexogyglucose transport in mixed, glial and enriched neuronal hippocampal cultures; (d) potentially, ascorbate, by acting as an electron donor, could impair the function of molecules involve in the transport or metabolism of glucose. We observed mild inhibition of glucose transport by one unrelated electron donor (glutathione). Moreover, transport was also inhibited by an ascorbate analog which is not an electron donor. Thus, we conclude that ascorbate transport in hippocampal neurons and glia occurs independent of the glucose transporter but that, nevertheless, ascorbate, at concentrations generally thought to be supraphysiological, has the potential for disrupting glucose transport.
Patel
M
M
Department of Biological Sciences, Gilbert Laboratory, MC 4020, Stanford University, Stanford, CA 94305, USA.
McIntosh
L
L
Bliss
T
T
Ho
D
D
Sapolsky
R
R
D000818:Animals; D001205:Ascorbic Acid / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology; D001930:Brain Injuries / Q000378:metabolism / Q000503:physiopathology; D002250:Carbon Radioisotopes / Q000378:metabolism; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D003683:Dehydroascorbic Acid / Q000378:metabolism*; D003847:Deoxyglucose / Q000378:metabolism; D004347:Drug Interactions / Q000502:physiology; D005333:Fetus; D005947:Glucose / Q000378:metabolism*; D051272:Glucose Transporter Type 1; D005978:Glutathione / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D009004:Monosaccharide Transport Proteins / Q000187:drug effects / Q000378:metabolism*; D009410:Nerve Degeneration / Q000378:metabolism / Q000503:physiopathology; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology; D051381:Rats
D002250:Carbon Radioisotopes; D051272:Glucose Transporter Type 1; D009004:Monosaccharide Transport Proteins; C495679:Slc2a1 protein, rat; C011669:ascorbate-2-phosphate; D003847:Deoxyglucose; D005978:Glutathione; D005947:Glucose; D001205:Ascorbic Acid; D003683:Dehydroascorbic Acid