Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0086543 (cataract)
 29,165 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The human arylamine N-acetyltransferases NAT1 and NAT2 are important xenobiotic-metabolizing enzymes involved in the detoxification and metabolic activation of numerous drugs and chemicals. NAT activity depends on genetic polymorphisms and on environmental factors. It has been shown that low NAT-acetylation activity could increase the risk of age-dependent cataract, suggesting that NAT detoxification function may be important for lens cells homeostasis. We report here that the NAT acetylation pathway may occur in human lens epithelial (HLE) cells. Functional NAT1 enzyme was readily detected in HLE cells by reverse transcription-polymerase chain reaction, Western blotting, and enzyme activity assays. NAT2 mRNA and enzymic activity were also detected. We investigated whether oxidants, known to be produced in HLE cells during oxidative stresses and involved in age-dependent cataract formation, decreased endogenous NAT1 and NAT2 activity. The exposure of HLE cells to peroxynitrite led to the dose-dependent irreversible inactivation of both NAT isoforms. Exposing HLE cells to continuously generated H(2)O(2) gave a dose-dependent inactivation of NAT1 and NAT2, reversible on addition of high concentrations of reducing agents. UVB irradiation also induced the reversible dose-dependent inactivation of endogenous NAT1 and NAT2, reversible on addition of reducing agents. Thus, our data suggest that functional NAT1 and NAT2 are present in HLE cells and may be impaired by oxidants produced during oxidative and photooxidative stresses. Oxidative-dependent inhibition of NATs in these cells may increase exposure of lens to the harmful effects of toxic chemicals that could contribute to cataractogenesis over time.
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PMID:The xenobiotic-metabolizing enzymes arylamine N-acetyltransferases in human lens epithelial cells: inactivation by cellular oxidants and UVB-induced oxidative stress. 1564 93

Free radicals and oxidative damage play roles in aging and age-related ocular diseases such as cataracts, so defensive mechanisms become important factors for protection. Because N-acetylation is involved in a wide variety of detoxification processes, this study was conducted to examine the relationship between the acetylator phenotypes and genotypes in a group of patients with age-related cataract. Sixty-one cases of age-related cataract and 104 controls were included in this study. Blood was collected in EDTA-containing tubes, and genomic DNA was extracted from the white blood cells by high pure PCR template preparation kit. Genotyping of NAT2 polymorphisms were detected by using a LightCycler-NAT2 mutation detection kit in real-time PCR. There was a significant difference in the distribution of the NAT2*6A acetylator phenotype between cases and the controls. The odds ratio of cataract for the NAT2*6A slow phenotype was 3.8 (95% CI = 1.08 to 13.11, p = 0.032) compared with the fast type. Our results suggest that slow acetylators are at higher risk of developing age-related cataracts than fast acetylators. As NAT2 is an important xenobiotic-metabolizing enzyme and theoretically xenobiotics such as ultraviolet B radiation, smoking, and alcohol use may induce cataract formation, NAT2 gene polymorphisms may be associated with genetic susceptibility of cataract.
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PMID:N-acetyltransferase 2 phenotype may be associated with susceptibility to age-related cataract. 1625 Nov 20

2,4,6-Trinitrotoluene (TNT) is an important occupational and environmental pollutant. In TNT-exposed humans, notable toxic manifestations have included aplastic anaemia, toxic hepatitis, cataracts, hepatomegaly, and liver cancer. Therefore, methods were developed to biomonitor workers exposed to TNT. The workers were employed in a typical ammunition factory in China. The external dose (air levels and skin exposure), the internal dose (urinary metabolites), the biologically effective dose (haemoglobin adducts, urinary mutagenicity), biological effects (chromosomal aberrations and health effects), and individual susceptibility (genotypes of xenobiotic-metabolizing enzymes) were determined. Haemoglobin-adducts of TNT, 4-amino-2,6-dinitrotoluene (4ADNT) and 2-amino-4,6-dinitrotoluene (2ADNT), and the urinary metabolites of TNT, 4ADNT and 2ADNT, were found in all workers and in some controls. The levels of the haemoglobin-adducts or the urinary metabolites correlated weakly with the skin or air levels of TNT. The urinary mutagenicity determined in a subset of workers correlated strongly with the levels of 4ADNT and 2ADNT in urine. The haemoglobin-adducts correlated moderately with the urinary metabolites and with the urinary mutagenicity. The genotypes of glutathione S-transferases (GSTM1, GSTT1, GSTP1) and N-acetyltransferases (NAT1, NAT2) were determined. In general, the genotypes did not significantly influence the haemoglobin-adduct levels and the urine metabolite levels. However, TNT-exposed workers who carried the NAT1 rapid acetylator genotype showed an increase in urinary mutagenicity and chromosomal aberrations as compared with slow acetylators. The haemoglobin adduct 4ADNT was significantly associated with a risk of hepatomegaly, splenomegaly and cataract; urine metabolites and genotypes were not associated with health effects. These results indicate that a set of well-selected biomarkers may be more informative regarding exposure and effect than routinely performed chemical measurements of pollutants in the air or on the skin.
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PMID:Comparison of biomarkers in workers exposed to 2,4,6-trinitrotoluene. 1743 51