Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.1.1.17 (ornithine decarboxylase)
 6,351 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The inhibitory effects of alcohol on hepatic growth in adults raises the possibility that the liver may be involved in fetal alcohol syndrome (FAS) in infants. To test this hypothesis, pregnant Sprague-Dawley rats were fed liquid diets containing either ethanol as 36% of the total calories, or were allowed ad libitum feeding of a control liquid diet (controls) throughout pregnancy. Other dams were exposed to the ethanol diet only during the first or last half of pregnancy. Pups delivered of dams exposed to the various diets (N = 40-45/group) were killed at 1, 3, 7, and 14 days of age. In addition to brain weights, crown-rump lengths, and facial features, the following parameters of liver development were documented; liver weight, liver/body weight ratio, liver histology, hepatic ornithine decarboxylase activity (ODC), hepatic protein content, and rate of hepatic DNA synthesis (as determined by [3H]thymidine incorporation). The results revealed that pups exposed to ethanol throughout pregnancy but not ad libitum control diet pups had brain weights, crown-rump lengths, and facial features in keeping with FAS. With respect to liver development, the livers in FAS pups were consistently smaller than in the control group. However, total body weights were decreased to a greater extent, such that when corrected for body weights, the smaller livers in FAS pups only became significant on day 14 of life. Liver histology was similar in the two groups with no signs of active inflammation or fibrosis. Hepatic ODC activity was also similar, indicating no impairment in polyamine synthesis. Hepatic DNA synthesis rates were decreased in FAS pups at all time intervals. Pups delivered of dams exposed to ethanol during either the first or last half of pregnancy had results comparable to those of controls. To identify the mechanism(s) responsible for these findings, a second series of experiments was performed wherein the hepatic expression of the following factors associated with liver development were documented by northern-blot analyses; growth hormone receptor (GHr), insulin-like growth factor-I (IGF-I) and -II (IGF-II) and IGF binding proteins (IGFBPs) 1, 2, 3, and 4 mRNA on gestational days 16 and 20 and postpartum days 1 and 7. In this series, a third group of pups derived from dams in whom caloric consumption was matched to that of the ethanol-fed dams (isocaloric controls) were also studied. The results revealed no consistent differences in GHr, IGF, or IGFBP mRNA expression in the three groups. In conclusion, liver development and hepatic DNA synthesis were significantly impaired in this animal model of FAS. That impairment, however, was not associated with decreases in either polyamine synthesis or disturbances in the hepatic component of the GH/IGF/IGFBP axis.
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PMID:Liver development in a rat model of fetal alcohol syndrome. 1199 7

Cell hydration changes play a key role in the regulation of cell function and critically affect insulin sensitivity of carbohydrate- and protein metabolism. Here, the modulation of gene expression profiles by hyperosmolarity and insulin was examined in H4IIE rat hepatoma cells by cDNA/oligonucleotiode array-, Northern- and Western blot analysis. Osmosensitive expression of the insulin-like growth factor binding protein Igfbp1, the multidrug resistance protein Mrp5 (Abcc5a) and cyclin D1 (Ccnd1) was established at the mRNA and protein level. Despite a hyperosmotic increase of cyclin D1 mRNA induction by insulin, the cyclin D1 protein expression was decreased by hyperosmolarity, suggesting a hyperosmotic interference with cyclin D1 mRNA translation. Hyperosmolarity at the mRNA level blunted the insulin response of betaine homocysteine-S-methyl transferase, the multidrug resistance proteins Mdr1a (Abcb1a) and 2 (Abcb4), the Igfbp 2 and 5, cyclin G1, dual specificity phosphatase Dusp1, signal transducers and activators of transcription Stat3 and 5, catalase and the bile salt export pump Bsep (Abcb11), whereas the insulin response was increased for Mrp5, cyclin D1 and the phosphoenolpyruvate carboxykinase. Insulin effects on the mRNA expression of the eukaryotic initiation factor 4E binding protein 4e-bp1, tubulin, gene 33, growth hormone receptor, keratin18, ornithine decarboxylase and heme oxygenase 1 were largely insensitive to hyperosmolarity. The data indicate that hyperosmolarity differentially modulates insulin sensitivity at the level of gene expression.
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PMID:Modulation of gene expression profiles by hyperosmolarity and insulin. 1776 65