Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:6.5.1.2 (DNA ligase)
 2,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Exposure of human nasal ciliated epithelium to reactive oxidants generated by the enzymatic xanthine-xanthine oxidase superoxide/hydrogen peroxide (H2O2) and glucose-glucose oxidase H2O2-generating systems, or to reagent H2O2 or hypochlorous acid (HOCl) resulted in significant alterations in ciliary beating. The earliest change noted was the presence of ciliary slowing, progressing eventually to complete ciliary stasis in some areas. Ciliary dyskinesia was seen within the first hour, often from as early as 15 min after exposure of the cells to reactive oxidants. Using peroxidases, various antioxidant enzymes, and oxidant scavengers, we confirmed that these detrimental effects on ciliary function were mediated primarily by H2O2 and HOCl. Moreover, 3-aminobenzamide (3-ABA), an inhibitor of the DNA repair enzyme poly ADP ribose polymerase, prevented H2O2-mediated inhibition of ciliary function, indicating that oxidant-mediated damage to DNA may well be the basis of the effects of H2O2 on ciliated epithelium. Acute and chronic inflammatory responses may therefore present the possible threat of H2O2- or HOCl-inflicted injury on bystander respiratory epithelium, leading to ciliary dyskinesia and slowing.
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PMID:Oxidant-mediated ciliary dysfunction in human respiratory epithelium. 795 61

V79mut1 cells are resistant to the toxic effects of 5-hydroxymethyl-2'-deoxyuridine (hmdUrd) and are deficient in the DNA repair enzyme hydroxymethyluracil-DNA glycosylase (hmUDG). We have therefore proposed that the toxicity of hmdUrd results from the repair of the lesion from DNA. In order to clarify the biological role of hmUDG, we have determined whether the repair-deficient cells showed resistance or sensitivity to the toxic or mutagenic effects of other DNA-damaging agents. Cells were exposed to hmdUrd, ionizing or ultraviolet radiation, to the alkylating agent MNNG, and to oxidative stress produced by hypoxanthine/xanthine oxidase, glucose/glucose oxidase, nitric oxide donor SNAP, or to H2O2. The V79mut1 cells did not show increased mutagenesis in response to hmdUrd. Relative to the V79 parent cells, the V79mut1 cells were not markedly altered in sensitivity to oxidizing agents and ionizing radiation (which produce hmdUra in DNA). The repair-deficient cells wee equally sensitive as the parent V79 cells to DNA damage induced by ultraviolet radiation or by MNNG. No significant differences were seen between the parent and the repair-deficient cells in terms of synthesis of poly(ADP-ribose) in response to damage or in their sensitization to 3-aminobenzamide. Thus, the loss of the 5-hydroxymethyluracil (hmUra)-DNA glycosylase activity in mammalian cells in culture confers no obvious deleterious effect on cell survival or mutagenicity in response to a wide range of DNA damage. These studies indicate that the major lesion known to be repaired by hmUra-DNA glycosylase, an hmUra residue replacing thymine, is produced in cells only in small quantities as the result of exposure to common DNA-damaging agents. These results raise the possibility that hmUra-DNA glycosylase may have evolved to respond to other lesions than hmUra residues formed from the oxidation of thymine.
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PMID:Lack of phenotypic alteration of hmUra-DNA glycosylase-deficient hamster cells exposed to DNA-damaging agents. 910 Aug 52