Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The induced activity of aryl hydrocarbon hydroxylase (AHH), measured by the metabolism of benzo[a]pyrene to fluorescent products in cultured human lymphocytes, shows a strong seasonal variation. The in vivo metabolism of antipyrine, which is also catalyzed by microsomal cytochrome P-450-dependent monooxygenases, has been reported to be correlated with AHH inducibility in human lymphocytes. To determine whether antipyrine metabolism also showed seasonal changes, we measured antipyrine half-life (t 1/2) in 10 nonsmokers and eight smokers at the two times of the year that correspond to the high and low peaks of inducible AHH activity as measured in lymphocytes. The mean antipyrine t 1/2 determined in all 18 subjects in summer was almost identical to that found in winter (mean +/- SEM = 10.90 +/- 0.65 and 10.96 +/- 0.78 hr). AHH activity in cultured human lymphocytes from the nonsmoking subjects was determined in control and 3-methylcholanthrene-induced cells to obtained inducibility ratios of 4.2 +/- 0.56 (SEM) in the summer and 1.4 +/- 0.14 (SEM) in winter. These results indicate that the seasonal variation in AHH inducibility in human lymphocytes is not reflected by a corresponding seasonal variation in antipyrine metabolism in vivo.
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PMID:Absence of seasonal variation in antipyrine metabolism. 705 21

We have generated transgenic mice expressing the human apolipoprotein CII (apoCII) gene under the transcriptional control of the human cytochrome P-450 IA1 (CYPIA1) promoter. Human apoCII transgenic (HuCIITg) mice exhibited significant basal expression of the transgene (plasma apoCII level = 26.1 +/- 4 mg/dl) and showed further induction of transgene expression after treatment with beta-naphthoflavone. Unexpectedly, HuCIITg mice were hypertriglyceridemic and human apoCII levels correlated strongly to triglyceride levels (R = 0.89, P < 0.0001). Triglyceride levels (mg/dl +/- SEM) were elevated compared to controls in both the fed (804 +/- 113 vs 146 +/- 18, P < 0.001) and fasted (273 +/- 39 vs 61 +/- 4, P < 0.001) states. HuCIITg mice accumulated triglyceride-rich very low density lipoproteins (VLDL) with an increased apoC/apoE ratio. Tracer kinetic studies indicated delayed clearance of VLDL-triglyceride, and studies using Triton inhibition of VLDL clearance showed no increase in VLDL production. Plasma from these mice activated mouse lipoprotein lipase normally and radiolabeled VLDL were normally hydrolyzed. However, HuCIITg VLDL showed markedly decreased binding to heparin-Sepharose, suggesting that apoCII-rich, apoE-poor lipoprotein may be less accessible to cell surface lipases or receptors within their glycosaminoglycan matrices. HuCIITg mice are a promising model of hypertriglyceridemia that suggests a more complex role for apoCII in the metabolism of plasma triglycerides.
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PMID:Overexpression of apolipoprotein CII causes hypertriglyceridemia in transgenic mice. 816 69

The present project assessed the effect of environmental contamination with polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs), and biphenyls (PCBs) on hepatic microsomal ethoxyresorufin O-deethylase (EROD) activities and morphological parameters in matched double-crested cormorant (Phalacrocorax auritus) hatchlings from egg clutches chosen for chemical analysis. Double-crested cormorant eggs were collected from five colonies across Canada, with differing levels of contamination. Levels of contamination expressed in sum of 2,3,7,8-tetrachlorodibenzo-p-dioxin-toxic equivalents (TCDD-toxic equivalents or TEQ, ng/kg egg; mean +/- SEM) were: Saskatchewan, 250 +/- 50; Chain Islands, 672 +/- 73; Christy Islet, 276 +/- 14; Crofton, 131, n = 1; and Lake Ontario, 1606 +/- 118. In the hatchlings, hepatic EROD activities (pmol/min/mg protein; mean +/- SEM) were: Saskatchewan, 283 +/- 42; Chain Islands, 516 +/- 98; Christy Islet, 564 +/- 91; Crofton, 391 +/- 52; and Lake Ontario, 2250 +/- 156. Hepatic microsomal EROD activity (pmol/min/mg protein) regressed positively on TEQ (r2 = .69; p < .00005; n = 25). Yolk weight (g) regressed negatively on TEQ (r2 = .44; p = .00005). Wing length (mm) regressed negatively on PCB-169 (r2 = .28; p = .007). Monospecific antibodies raised against rat cytochrome P-450 1A1 recognized a protein in the hepatic microsomes of the double-crested cormorant, and also in those of the great blue heron (Ardea herodias), using immunoblotting. The intensity of the stained band increased with increased EROD activity, supporting the assumption that ethoxyresorufin is a suitable substrate for avian cytochrome P-450 1A1. These results validate the use of avian hepatic microsomal EROD activity as an index of cytochrome P-450 1A1 induction by environmental levels of polychlorinated aromatic hydrocarbons and as a useful screening tool to determine the extent of exposure to such chemicals. Furthermore, the induction of cytochrome P-450 1A1 observed in the cormorant indicates that the Ah receptor-mediated process, by which TCDD and related chemicals exert many of their toxicities, has been activated.
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PMID:Biological effects of polychlorinated dibenzo-p-dioxins, dibenzofurans, and biphenyls in double-crested cormorant chicks (Phalacrocorax auritus). 830 2

Metabolic inactivation of all-trans retinoic acid to 4-hydroxy retinoic acid occurs via a cytochrome P-450 enzyme. We investigated the effects of liarozole on the retinoic acid 4-hydroxylase activity of human epidermis and its ability to modify in vivo human skin responses to retinoic acid and all-trans retinol. Retinoic acid 4-hydroxylase activity induced in vivo by 4 d treatment with retinoic acid (0.1%) was inhibited in vitro by liarozole in a concentration-dependent manner. Comparable micromolar concentrations of liarozole were extracted from stratum corneum-free epidermis treated with 3% liarozole. Retinoic acid levels in liarozole-treated skin increased to 19 +/- 5 ng/g wet wt (mean +/- SEM, p < 0.002, n = 17) at 18 h and to 6 +/- 2 ng/g wet wt (p = 0.38, n = 17) at 48 h as compared to vehicle (not detectable). At 48 h, retinoic acid 4-hydroxylase activity was induced 9-fold over vehicle (p < 0.03, n = 8). At 96 h, no significant erythema or increased epidermal thickness was found when either retinoic acid (0.001%), all-trans retinol (0.0250%), or liarozole (3%) was applied individually, but when 0.001% retinoic acid and 3% liarozole were applied together, both erythema and increased epidermal thickness occurred. In contrast, 0.025% all-trans retinol and 3% liarozole together caused increased epidermal thickness but no erythema. These data demonstrate that, at doses used here, liarozole, although an effective inhibitor of retinoic acid 4-hydroxylase, cannot function alone like a retinoid in vivo, probably because of retinoic acid 4-hydroxylase induction. In the presence of a low dose retinoic acid or all-trans retinol, however, liarozole can amplify human skin responses to each retinoid in a manner characteristic of the retinoid at a higher dose (erythema and hyperplasia with retinoic acid; no erythema but hyperplasia with all-trans retinol).
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PMID:Liarozole inhibits human epidermal retinoic acid 4-hydroxylase activity and differentially augments human skin responses to retinoic acid and retinol in vivo. 875 60


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