Oxidative Stress and the CNS

Re: What about the transporters?

On Mon Dec 14, grover wrote
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>Dr. Rice: In response to the question by Dr. Juurlink - I did not understand that the cellular concentration of ascorbate was determined mainly by its ability to reduce DHA to ascorbate. I had always thought the number of ascorbate transporters was the key determinant.
>akg

>On Mon Dec 14, Bernhard H.J. Juurlink wrote
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>>Dr, Rice,
>> One thing that puzzles me is why neurons which have a poor ability to reduce oxidized-ascorbate (because of their relatively oxidized cytosol) should have an order of magnitude more ascorbate than astrocytes which have a very good ability to reduce oxidized-ascorbate. Is there any evidence for ascorbate metabolic coupling between neurons and astrocytes with oxidized-ascorbate transferred from neurons to astrocytes and reduced-ascorbate transferred from astrocytes to neuron? It is known that the glucose transporters transport oxidized-ascorbate and there would be a concentration gradient differential tending to move oxidized-ascorbate out of the neuron to the extracellular space and from there to the astrocyte. What about the movement of reduced-ascorbate in the other direction?

>>Why should there be so much ascorbate in neurons? Does it have a function other than reducing oxidized-tocopherol? What would this be? BJ
>

Dr. Grover -- Dr. Juurlink is probably referring to several studies that have shown that the ascorbate oxidation product, dehydroascorbate, can be transported by the glucose transporter in some cell types. I do not know if this has been shown for brain cells. While this CAN happen, it is not clear that it DOES happen as a physiologically important path in vivo. Our laboratory and others find evidence for an ascorbate transporter in brain tissue. We cannot maintain tissue levels in vitro when ascorbate is oxidizing in the incubation media. But when media levels of ascorbate are stabilized in the reduced state (confirmed by HPLC), brain slices take up ascorbate to normal physiological levels. I agree with you that active ascorbate transport is the primary factor governing cellular ascorbate contents. Once in the intracellular compartment, ascorbate is maintained in the reduced form, presumably by thiols in the cytosol, in concert with the rest of the antioxidant network.

Tue Dec 15