Differential regulation of hydrogen peroxide and Fas-dependent apoptosis pathways by dehydroascorbate, the oxidized form of vitamin C.
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.
Puskas
Ferenc
F
Department of Medicine, State University of New York Upstate Medical University, College of Medicine, 750 East Adams Street, Syracuse, NY 13210, USA.
Gergely
Peter
P
Niland
Brian
B
Banki
Katalin
K
Perl
Andras
A
D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000378:metabolism*; D017209:Apoptosis / Q000502:physiology*; D001205:Ascorbic Acid / Q000737:chemistry / Q000378:metabolism*; D003683:Dehydroascorbic Acid / Q000378:metabolism* / Q000494:pharmacology; D005434:Flow Cytometry; D016166:Free Radical Scavengers / Q000737:chemistry / Q000378:metabolism; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D019169:Jurkat Cells / Q000187:drug effects / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008928:Mitochondria / Q000378:metabolism; D016877:Oxidants / Q000378:metabolism*; D010084:Oxidation-Reduction; D010734:Phosphogluconate Dehydrogenase / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D014153:Transaldolase / Q000378:metabolism; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000378:metabolism*
D000975:Antioxidants; D016166:Free Radical Scavengers; D016877:Oxidants; D017382:Reactive Oxygen Species; D019014:fas Receptor; D006861:Hydrogen Peroxide; D010734:Phosphogluconate Dehydrogenase; D005954:Glucosephosphate Dehydrogenase; D014153:Transaldolase; D005978:Glutathione; D001205:Ascorbic Acid; D003683:Dehydroascorbic Acid