Disease relevance of DEHYDROASCORBIC ACID

• The virion-derived protein, as well as a recombinant form expressed in Escherichia coli, exhibited thioltransferase and dehydroascorbate reductase activities indicative of a functional GRX [1].
• Glutaredoxin homolog encoded by vaccinia virus is a virion-associated enzyme with thioltransferase and dehydroascorbate reductase activities [1].
• Human HL-60 myeloid leukemia cells transport dehydroascorbic acid via the glucose transporters and accumulate reduced ascorbic acid [2].
• Relationship of dehydroascorbic acid transport to cell lineage in lymphocytes from normal subjects and patients with chronic lymphocytic leukemia [3].
• Melanoma cell lines transported dehydroascorbic acid at a rate that was at least 10 times greater than the rate of transport by melanocytes, whereas both melanoma cells and melanocytes transported ascorbate with similar efficiency [4].

Psychiatry related information on DEHYDROASCORBIC ACID

• In senile dementia patients, ascorbic acid and dehydroascorbic acid levels were also measured in the cerebrospinal fluid [5].

High impact information on DEHYDROASCORBIC ACID

• Here we use the Xenopus laevis oocyte expression system to show that the mammalian facilitative hexose transporters are efficient transporters of the oxidized form of vitamin C (dehydroascorbic acid) [6].
• Dehydroascorbate reductase (DHAR) catalyzes the reduction of dehydroascorbate (oxidized ascorbate) to Asc and thus contributes to the regulation of the Asc redox state [7].
• Vitamin C is a kinase inhibitor: dehydroascorbic acid inhibits IkappaBalpha kinase beta [8].
• Human monocytes were found to have a greater capacity to take up dehydroascorbic acid than neutrophils, related to more facilitative glucose transporters on the monocyte cell membrane [9].
• In HL-60 neutrophils, GM-CSF increased both the transport of dehydroascorbic acid and the intracellular accumulation of ascorbic acid [9].

Chemical compound and disease context of DEHYDROASCORBIC ACID

• The 125-residue Grx domain and the two full-length variants were expressed in E. coli and exhibited GSH-dependent hydroxyethyl disulfide and dehydroascorbate reducing activities [10].
• When NO-catalyzed degradation of HS was depressed in mouse neuroblastoma cell line (N2a) by using 3-beta[2(diethylamino) ethoxy]androst-5-en-17-one (U18666A), both ascorbate and dehydroascorbic acid restored formation of anMan-positive products that colocalized with Rab7 [11].
• The contents of catalytic Fe, which is critical for H2O2-dependent hydroxyl radical (OH) production, and the oxidized forms of ascorbate and glutathione pools, dehydroascorbate (DHA) and oxidized glutathione (GSSG), markedly increased, a significant oxidative damage to lipids and proteins took place under the moderate water stress [12].
• Pretreatment with ABA caused an obvious reduction in the content of catalytic Fe and significant increases in the activities of antioxidant enzymes and the contents of non-enzymatic antioxidants, and then significantly reduced the contents of DHA and GSSG and the degrees of oxidative damage in leaves exposed to the moderate water stress [12].
• Pretreatment with an ABA biosynthesis inhibitor, tungstate, significantly suppressed the accumulation of ABA induced by water stress, reduced the enhancement in the capacity of antioxidant defense systems, and resulted in an increase in catalytic Fe, DHA and GSSG, and oxidative damage in the water-stressed leaves [12].

Biological context of DEHYDROASCORBIC ACID

• In vitro mutagenesis studies in Xenopus laevis oocytes demonstrated significant decreases in the transport of 3-O-methyl-D-glucose and dehydroascorbic acid [13].
• The increased sensitivity to oxidative stress was largely reversed when glutathione-depleted cells were preloaded with ascorbic acid by exposure to dehydroascorbic acid [14].
• Ascorbate and dehydroascorbate influence cell cycle progression in a tobacco cell suspension [15].
• Dehydroascorbate uptake activity correlates with cell growth and cell division of tobacco bright yellow-2 cell cultures [16].
• A combination of dehydroascorbic acid and hydroxycobalamin (vitamin B-12) inhibited mitoses of tumors in mice [17].

Anatomical context of DEHYDROASCORBIC ACID

• We investigated the transport of vitamin C in its oxidized form (dehydroascorbic acid) via GLUT1 into erythrocytes of 2 patients with GTPS [18].
• Neither dehydroascorbate nor isoascorbate increases HL-60 cell growth [19].
• Mice with established hematopoietic and epithelial cell xenografts were studied for the accumulation of injected ascorbic acid and dehydroascorbic acid [20].
• Dehydroascorbate uptake as an in vitro biochemical marker of granulocyte differentiation [21].
• GSH-dependent dehydroascorbate reductase activity in liver cytosol was variable, but typically 2-3-fold that of NADPH-dependent activity [22].

Associations of DEHYDROASCORBIC ACID with other chemical compounds

• Additional studies using HL-60 cells induced to differentiate with dimethyl sulfoxide or 12-O-tetradecanoylphorbol-13-acetate support the view that a major increase in dehydroascorbate uptake in cultured granulopoietic progenitors is a manifestation of a neutrophil differentiation [21].
• The data reveal a novel mechanism for increasing glutathione levels through stimulation of the pentose phosphate pathway and identify dehydroascorbate as an antioxidant for cells susceptible to the pro-oxidant and proapoptotic properties of vitamin C [23].
• HL-60 cells do not depend on glutathione to transport or reduce dehydroascorbic acid [14].
• These data indicate that monodehydroascorbate mediates inhibition of HMG-CoA reductase by both ascorbate and dehydroascorbate [24].
• In these microsomes, the amount of protein-disulfide isomerase was similar, but the availability of protein thiols was different and correlated with dehydroascorbate uptake [25].

Gene context of DEHYDROASCORBIC ACID

• We demonstrated that vitamin C inhibits DNA synthesis in HeLa cells and, mainly the form of dehydroascorbic acid (DHA), delays the entry of p53-deficient synchronized HeLa and T98G cancer cells into mitosis [26].
• Pre-incubation with dehydroascorbic acid resulted in reduced intracellular ROS levels and inhibition of MAPK activation induced by the above treatments [27].
• The mammalian Trx system is a dehydroascorbic acid reductase recycling ascorbic acid essential for cell functions [28].
• We found that GSTO2-2 has activity with the same substrates as GSTO1-1, and the dehydroascorbate reductase activity of GSTO2-2 is approximately 70-100-fold higher than that of GSTO1-1 [29].
• All cloned and expressed candidates exhibited relatively high thiol transferase and dehydroascorbate reductase activities and low activity towards 1-chloro-2,4-dinitrobenzene, characteristic of Omega class GSTs, whereas only CG6781 catalysed the synthesis of PDA in vitro [30].

Analytical, diagnostic and therapeutic context of DEHYDROASCORBIC ACID

• In itself, dehydroascorbate did not affect cytosolic or mitochondrial reactive oxygen intermediate levels as monitored by flow cytometry using oxidation-sensitive fluorescent probes [23].
• Ascorbate and dehydroascorbate transport was investigated in rat liver microsomal vesicles using radiolabeled compounds and a rapid filtration method [31].
• Ascorbic acid and dehydroascorbic acid were determined by using HPLC with coulometric electrochemical detection, and protein binding was determined by centrifugal ultrafiltration [32].
• The method uses microvial sampling, derivatization with 4,5-dimethyl-1,2-phenylenediamine, capillary electrophoresis separation, and laser-induced fluorescence detection and quantifies the ascorbic acid and dehydroascorbic acid levels with less than a 15-min total analysis time including sample preparation and derivatization [33].
• Dehydroascorbic acid reduction was at least 5-fold greater in neutrophil lysates than in myeloid tumour cell lysates, and glutaredoxin was detected in normal neutrophil lysates but not in myeloid tumour cell lysates by Western blotting [34].

References