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Accumulation of intracellular ascorbate from dehydroascorbic acid by astrocytes is decreased after oxidative stress and restored by propofol
Author(s) -
Daskalopoulos Rina,
Korcok Jasminka,
Tao Lei,
Wilson John X.
Publication year - 2002
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.10099
Subject(s) - dehydroascorbic acid , glutathione , intracellular , ascorbic acid , oxidative stress , biochemistry , buthionine sulfoximine , antioxidant , chemistry , vitamin c , enzyme , food science
Primary rat astrocyte cultures absorbed dehydroascorbic acid from the medium and reduced it to intracellular ascorbate. Uptake of dehydroascorbic acid (5–200 μM) was inhibited only partially by glucose (10 mM). The remaining glucose‐insensitive component of dehydroascorbic acid uptake was inhibited reversibly by sulfinpyrazone (IC 50 = 80 μM). Dehydroascorbic acid uptake was not mediated by Na + ‐ascorbate cotransporters or volume‐sensitive anion channels because it was neither Na + ‐dependent nor blocked by the channel antagonist, 4,4′‐diisothiocyanatostilbene‐2,2′‐disulfonic acid. Oxidative stress, induced in astrocytes by the lipophilic radical generator tert‐butyl hydroperoxide, decreased intracellular glutathione concentration and inhibited accumulation of intracellular ascorbate from dehydroascorbic acid. Subsequent administration of either the native antioxidant alpha‐tocopherol (200 μM) or anesthetic concentrations of the antioxidant sedative propofol (1–8 μM, administered 30 min after tert‐butyl hydroperoxide), did not change glutathione concentration but restored the ability of astrocytes to accumulate intracellular ascorbate from dehydroascorbic acid. These results are consistent with a novel mechanism of astrocytic ascorbate accumulation that is inhibited by lipophilic radicals and protected by lipophilic antioxidants such as propofol. GLIA 39:124–132, 2002. © 2002 Wiley‐Liss, Inc.