Differential regulation of hydrogen peroxide and Fas-dependent apoptosis pathways by dehydroascorbate, the oxidized form of vitamin C

Abstract

Dehydroascorbate (DHA), the oxidized form of vitamin C (ascorbate), enhanced antioxidant defenses of human T cells preferentially importing DHA over ascorbate. In itself, DHA did not affect cytosolic or mitochondrial reactive oxygen intermediate levels as monitored by flow cytometry using oxidation-sensitive fluorescent probes. DHA at 200-1,000 microM stimulated activity of pentose phosphate pathway enzymes glucose 6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, and transaldolase, elevated intracellular glutathione levels, and inhibited H(2)O(2)-induced changes in mitochondrial transmembrane potential and cell death. With respect to the CD4 antigen, DHA selectively enhanced cell-surface expression of the Fas receptor and increased susceptibility of Jurkat and H9 human T cells to Fas-mediated cell death. The data identify DHA as a selective regulator of H(2)O(2)- and Fas-dependent apoptosis pathways.