Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.17.3.2 (xanthine oxidase)
 8,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Repair of DNA lesions induced by oxygen radicals, generated by xanthine/xanthine oxidase (X/XO), was studied in human peripheral blood lymphocytes and in PHA-stimulated proliferating lymphocytes from 4 healthy subjects. The lesions included DNA-strand breaks (SSB) and other lesions that are converted to SSB under alkaline conditions. The frequencies of SSB were estimated by fluorometric analysis of DNA unwinding. Maximum production of SSB occurred within 10 min of incubation with X/XO at 22 degrees C; with 0.5 mM or higher concentrations of xanthine; and with 0.1-0.5 units/ml of xanthine oxidase. Proliferating lymphocytes repaired X/XO-induced SSB about 4 times more rapidly than lymphocytes. Lymphocytes repaired X/XO-induced SSB more slowly than SSB caused by gamma-radiation. These findings are consistent with the evidence that a number of DNA-repair enzymes have greater activity in proliferating cells than in resting cells. These findings also support the view that there are differences between the DNA damage due to oxygen radicals and that due to ionizing radiation.
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PMID:Repair of DNA damage induced by oxygen radicals in human non-proliferating and proliferating lymphocytes. 137 2

Because protein-malnourished or endotoxemic patients are at an increased risk of developing nosocomial infections, this study was performed to investigate the effects of protein malnutrition and endotoxemia, alone and in combination, on systemic and intestinal immunity. Protein malnutrition was created by feeding the animals a solid diet containing 0.03% protein. Subgroups of these protein-malnourished mice were killed after being challenged with saline or endotoxin on days 0, 7, 14, or 21. At death, the animals were weighed, tissues were harvested for histologic analysis (ileum, mesenteric lymph node [MLN], liver, and spleen), mitogen responsiveness (MLN, Peyer's patches, and spleen), and xanthine oxidase measurements (ileum and cecum). Separate groups were evaluated for survival. Both the saline and endotoxin-challenged mice had lost about 30% of their body weight after 21 days on the low-protein diet. The protein-malnourished mice were more susceptible to endotoxin-induced mortality (70% at 21 days) than the normally nourished mice (0%) (p less than .001). The mitogen responsiveness of the protein-malnourished mice to the T-cell mitogens (PHA and Con-A) progressively decreased the longer the mice were protein malnourished, and this decreased in blastogenic responsiveness was associated with histologic evidence of lymphoid atrophy. In contrast, the blastogenic response to the primarily B-cell mitogen, PWM, was largely preserved. The endotoxin challenge further depressed the immune state of mice tested after 0, 7, or 14 (but not 21) days of protein malnutrition. Thus, both protein malnutrition and endotoxin impaired systemic and gut-associated immune responsiveness to mitogens. However, in the protein-malnourished mice, the degree of immune suppression did not correlate with endotoxin-induced mortality.
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PMID:Protein malnutrition alone and in combination with endotoxin impairs systemic and gut-associated immunity. 173 15

The metabolic causes for immune impairment in patients with severe chronic inflammatory diseases have not been clearly defined. Recently, the overproduction of poly(ADP-ribose) in resting lymphocytes with unrepaired DNA strand breaks has been suggested to contribute to immune dysfunction in adenosine deaminase-deficient patients. Our experiments have determined to what extent DNA damage and poly(ADP-ribose) synthesis might also explain the impaired mitogen responsiveness of PBL exposed to toxic oxygen species. Treatment of normal resting human lymphocytes with xanthine oxidase and hypoxanthine dose-dependently induced DNA strand breaks and triggered the rapid synthesis of poly(ADP-ribose). Subsequently, NAD+ and ATP pools decreased precipitously. Lymphocytes exposed previously to the enzymatic oxidizing system did not synthesize DNA after stimulation with PHA. However, if the medium was supplemented with 3-aminobenzamide or nicotinamide, two compounds that inhibit poly(ADP-ribose) formation, cellular NAD+ and ATP pools were preserved, and the lymphocytes responded vigorously to a mitogenic challenge. Excessive poly(ADP-ribose) synthesis, provoked by DNA strand breakage, may represent a common pathway that connects the immunodeficiency syndromes associated with (a) exposure of lymphocytes to toxic oxygen species during chronic inflammatory states, (b) adenosine deaminase deficiency, and (c) certain DNA repair disorders.
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PMID:Lymphocyte dysfunction after DNA damage by toxic oxygen species. A model of immunodeficiency. 395 May 45

We have studied the effect of oxidant stress on the lymphocyte membrane and lymphocyte functions. Lymphocyte cultures were incubated with xanthine oxidase and xanthine, an enzyme system known to generate several highly reactive oxygen compounds. We demonstrated that these lymphocytes were viable after exposure to an in vitro oxidant stress. However, there was a marked reduction in their ability to bind SRBCs and to form caps after Con A stimulation. These lymphocytes also demonstrated a delay in PHA-induced LBT, with maximal response occurring at 5 days instead of 3 days. Catalase, a hydrogen peroxide scavenger, protected lymphocytes from this injury, implicating hydrogen peroxide as the causative agent. Another lymphocyte membrane-related function, the ability to stimulate or respond in MLC, was not impaired after oxidant injury. These results demonstrate that after in vitro oxidant injury, lymphocytes may have alterations in the cell membrane and impaired function.
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PMID:The effect of oxidant injury on the lymphocyte membrane and functions. 645 85

The effect of histidine on damage induced by oxygen radicals was studied in peripheral blood lymphocytes treated with free oxygen radical-inducing agents: hydrogen peroxide, xanthine oxidase plus hypoxanthine, bleomycin and gamma-rays. L-Histidine, at a concentration of 1 mM, was found to potentiate both cell killing and inhibition of PHA-stimulated cell division brought about by hydrogen peroxide or xanthine oxidase plus hypoxanthine. In contrast, L-histidine did not affect gamma-ray- or bleomycin-induced cell killing and inhibition of PHA-stimulated cell division. We suggest that L-histidine potentiation of cell damage is mainly mediated by interaction of the amino acid with hydrogen peroxide and/or iron rather than with other reactive oxygen species. In addition, these results also indicate that hydrogen peroxide produced by gamma-radiation- or bleomycin-treated cells plays no role in the toxic effects elicited by these agents.
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PMID:Differential effect of L-histidine in human lymphocytes damaged by different oxygen radical producing systems. 768 Jul 58