Ascorbate (vitamin C) is found in high concentrations in the striatum in which it may play a role in behavioral activation. To test this hypothesis, freely behaving rats received bilateral intrastriatal infusions of ascorbate oxidase (AAO) to inactivate extracellular ascorbate. Slow-scan voltammetry was used simultaneously to assess changes in ascorbate and 3,4-dihydroxyphenylacetic acid (DOPAC...

Ruptured pea (Pisum sativum cv. Massey Gem) chloroplasts exhibited ascorbate peroxidase activity as determined by H(2)O(2)-dependent oxidation of ascorbate and ascorbate-dependent reduction of H(2)O(2). The ratio of ascorbate peroxidase to NADP-glyceraldehyde 3-phosphate dehydrogenase activity was constant during repeated washing of isolated chloroplasts. This indicates that the ascorbate perox...

Ascorbic acid is an essential nutrient commonly regarded as an antioxidant. In this study, we showed that ascorbate at pharmacologic concentrations was a prooxidant, generating hydrogen-peroxide-dependent cytotoxicity toward a variety of cancer cells in vitro without adversely affecting normal cells. To test this action in vivo, normal oral tight control was bypassed by parenteral ascorbate adm...

Activation of the transcription factor hypoxia-inducible factor (HIF)-1 allows solid tumors to thrive under conditions of metabolic stress. Because HIF-1 is switched off by hydroxylation reactions that require ascorbate, inadequate intracellular ascorbate levels could contribute to HIF-1 overactivation. In this study, we investigated whether the ascorbate content of human endometrial tumors [kn...

Ascorbic acid (vitamin C) has followed opaque paths in treating pharmacologic ascorbate. Because myeloma cells are iron-rich, increasmultiplemyeloma, and othermalignancies. Inmyeloma cells, ascorbate surprisingly depleted glutathione and potentiated arsenate trioxide efficacy. Because oral ascorbate at 1 g produces plasma saturation, this dose was selected with arsenate. Predictably, in small t...

To determine how ascorbic acid moves from the bloodstream into tissues, we assessed transfer of the vitamin across the barrier generated by EA.hy926 endothelial cells when these were cultured on semipermeable filter supports. Ascorbate transfer from the luminal to the abluminal compartment was time dependent, inhibited by anion channel blockers and by activation of protein kinase A, but was inc...

Iron and ascorbate are vital cellular constituents in mammalian systems. The bulk-requirement for iron is during erythropoiesis leading to the generation of hemoglobin-containing erythrocytes. Additionally; both iron and ascorbate are required as co-factors in numerous metabolic reactions. Iron homeostasis is controlled at the level of uptake; rather than excretion. Accumulating evidence strong...

During hibernation in Arctic ground squirrels (Spermophilus parryii), O(2) consumption and plasma leukocyte counts decrease by >90%, whereas plasma concentrations of the antioxidant ascorbate increase fourfold. During rewarming, O(2) consumption increases profoundly and plasma ascorbate and leukocyte counts return to normal. Here we investigated the dynamic interrelationships among these change...

Ascorbate (ascorbic acid, vitamin C), in pharmacologic concentrations easily achieved in humans by i.v. administration, selectively kills some cancer cells but not normal cells. We proposed that pharmacologic ascorbate is a prodrug for preferential steady-state formation of ascorbate radical (Asc(*-)) and H(2)O(2) in the extracellular space compared with blood. Here we test this hypothesis in v...