Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Hypoxic and hypercapnic ventilatory drives were measured in eight healthy male subjects before and after ingestion of ethanol, in a dose of 17 mmol/kg body weight. 2. A significant decrease in hypoxic ventilatory drive was observed at 20 min after ethanol (P less than 0.05). A significant depression in hypercapnic drive was observed at 70 min after indigestion of ethanol (P less than 0.05). The mean peak blood ethanol (24mmol/1) occurred at 20 min, at which time the lowest mean hypoxic drive was recorded. 3. Ethanol in moderate doses produced a depression of both hypoxic and hypercapnic ventilatory drives in normal subjects. This suggests that ethanol may play a role in the precipitation of acute respiratory failure in certain patients in whom the ventilatory drive is already impaired, as in chronic airways obstruction.
Clin Sci Mol Med 1975 Jul
PMID:Effect of ethanol on the ventilatory responses to oxygen and carbon dioxide in man. 114 93

Ethanol-inducible cytochrome P450 (P450IIE) is reported to be induced by ketosis. In the present study, the effects of a high fat diet on P450IIE induction and the relationship between ketone body concentration and P450IIE induction were studied by the following: 1) measurement of the activity of aniline hydroxylase, 2) immunoblot analysis for P450IIE protein, and 3) Northern blot analysis for P450IIE mRNA. The enzyme activities (aniline hydroxylase) in hepatic and renal microsomes were elevated about 2-3-fold by feeding with a high fat diet for 3 days. The increases in enzyme activities were also accompanied by 3-fold increases in immunoreactive P450IIE protein and its mRNA. In contrast, no differences were observed for the catalytic activities of N-alkoxyresorufin dealkylases or the amounts of immunoreactive P450IA and P450IIC, indicating a specific induction of P450IIE by high fat feeding. Furthermore, the increases in the levels of P450IIE mRNA correlated positively (r = 0.73) with plasma concentrations of acetoacetate and beta-hydroxybutyrate but not with that of acetone, which induces P450IIE without changing its mRNA level. Our data thus indicated that P450IIE induction during the ketosis of a high fat feeding appears to be due to pretranslational activation and that is similar to the induction mechanism of fasted and diabetic animals.
Mol Pharmacol 1992 Mar
PMID:Pretranslational activation of cytochrome P450IIE during ketosis induced by a high fat diet. 154 75

Ethanol inhibits adenosine uptake, thereby increasing the concentration of extracellular adenosine. Elevation of extracellular adenosine increases intracellular cAMP concentration via activation of adenosine A2 receptors. Extracellular adenosine is also required for the subsequent development of ethanol-induced heterologous desensitization. Here we report that activation of cAMP-dependent protein kinase is necessary for inhibition of adenosine uptake by ethanol and for the consequent accumulation of extracellular adenosine. Ethanol does not inhibit adenosine uptake in mutants of the S49 cell line that lack receptor-stimulated cAMP production (unc cells) or cAMP-dependent protein kinase activity (kin- cells). Forskolin, which bypasses the receptor-coupling defect in unc cells to increase cAMP levels, restores inhibition of adenosine uptake by ethanol. In contrast, in kin- cells forskolin did not restore inhibition of adenosine uptake by ethanol, despite similar increases in cAMP levels. Taken together, these results suggest that cAMP-dependent protein kinase phosphorylates a component of the nucleoside transporter, thereby regulating the sensitivity of adenosine transport to ethanol.
Mol Pharmacol 1991 Nov
PMID:cAMP-dependent protein kinase regulates inhibition of adenosine transport by ethanol. 165 11

Ethanol has been shown to inhibit N-methyl-D-aspartate (NMDA)-stimulated calcium influx into cerebellar granule cells grown in culture. Because NMDA-mediated responses are modulated by a number of substances, we investigated the effects of several of these agents on ethanol-induced inhibition of calcium flux. Ethanol (50 mM) inhibited NMDA-dependent Ca2+ influx by approximately 50%. The percentage of inhibition remained constant with increasing NMDA concentrations (5-250 microM). Increasing Mg2+ concentrations in the assay medium inhibited NMDA-stimulated calcium influx but the EC50 for Mg2+ was unchanged in the presence of ethanol. Glycine at concentrations of 0.3-100 microM potentiated the effects of NMDA. Glycine at concentrations in excess of 10 microM decreased ethanol-mediated inhibition of NMDA-stimulated calcium influx. D-Serine was shown to have effects similar to those of glycine, whereas L-serine was significantly less active in potentiating NMDA-stimulated activity and reversing the ethanol-induced inhibition of calcium influx. N-Methylglycine and L-leucine were ineffective in potentiating NMDA actions but high concentrations (1 mM) of N-methylglycine attenuated ethanol-induced inhibition, whereas L-leucine (1 mM) had no effect. High concentrations of N-methylglycine were shown to reduce glycine-induced enhancement at the NMDA receptor, whereas L-leucine did not affect the glycine response. Glycine did not affect kainate-stimulated calcium influx and did not alter the small amount of inhibition produced by ethanol in the response of the cells to kainate. The results demonstrate that the in vivo actions of ethanol on the NMDA systems of brain may be dependent on glycine concentrations at these receptor sites.
Mol Pharmacol 1990 Dec
PMID:Glycine site-directed agonists reverse the actions of ethanol at the N-methyl-D-aspartate receptor. 170 Dec 11

Ethanol administration to rats by ethanol vapor inhalation (14 days) results in a 40-50% reduction in the level of gamma-aminobutyric acidA (GABAA) receptor alpha 1 subunit mRNAs [4.4 and 4.8 kilobases (kb)] in the cerebral cortex. The level of alpha 2 subunit mRNA (8.0 kb) was also reduced by 29%, whereas there was no effect of prolonged ethanol exposure on the level of alpha 3 subunit mRNA (3.1 kb). Ethanol exposure did not alter the steady state levels of cerebral cortical glutamic acid decarboxylase or beta-actin mRNAs. Moreover, no alterations in the levels of total RNA, poly(A)+ RNA, or rRNA were observed, suggesting that the ethanol-induced reductions in GABAA receptor alpha 1 and alpha 2 subunit mRNAs were not the result of a generalized effect of ethanol administration on transcription or mRNA turnover. These ethanol-induced reductions in GABAA receptor alpha subunit mRNAs may underlie alterations in GABAA receptor function or number observed following prolonged ethanol exposure in rats.
Mol Pharmacol 1991 Feb
PMID:Prolonged ethanol inhalation decreases gamma-aminobutyric acidA receptor alpha subunit mRNAs in the rat cerebral cortex. 170

The additive drugs alcohol, morphine, cocaine, and amphetamine are each associated with the development of tolerance and physical dependence. Changes in gene expression occur in cell culture and in vivo with the administration of these centrally-acting drugs. This article reviews those experiments that have studied drug-induced alterations in gene transcription. Ethanol has diverse effects on the amounts of messenger RNA molecules within the central nervous system. Ion channels, neuropeptides, membrane receptors, and immediate early genes represent several regulated mRNAs. The effects are selective, however, as many other specific products are not altered. Evidence for a genetic predisposition to ethanol use reinforces the importance of the genotype. Opioids, cocaine, and amphetamine also affect gene transcription. Messenger RNAs studied have included many of those demonstrated to be altered by alcohol use. Interestingly, use of any of these drugs alters the expression of immediate early genes. These genes may represent an initial step in the pathway that leads to drug addiction. The composite of drug-induced changes in gene expression results in the cellular responses of tolerance and dependence. The characterization of these changes should provide a better understanding of the molecular mechanisms of drug addiction.
Mol Neurobiol 1991
PMID:The molecular biology of addictive drugs. 172 3

Chromosomal rearrangements, uniformly represented by very large deletions, were stimulated upon transiently exposing Escherichia coli cells with a defective lambda prophage to about 18% (v/v) ethanol. It was shown that the ethanol treatment induced deletion formation rather than enriching for ethanol-tolerant cells. The deletions in 435 mutants were mapped to 26 groups. Ethanol treatment changed the spectrum of deletions relative to those arising spontaneously, and stimulated the formation of deletions with endpoints in E. coli DNA flanking the lambda fragment. The promotion of deletion formation by ethanol involves the joining of distant, nonhomologous linear DNA segments, which can be considered an illegitimate recombination event; however, activity of the E. coli recA gene product was also required. Although spontaneous deletions arose in comparable cells defective for recA, the incidence of deletion formation in recA cells was not altered by ethanol. It is proposed that ethanol stimulates chromosomal rearrangements involving two oppositely oriented replication forks, since the localized deletions commonly removed or inactivated the chromosomal segment including the bidirectional lambda origin of replication. The results imply a novel mutagenic process induced by an agent that does not act directly on DNA.
Mol Gen Genet 1991 Dec
PMID:Mapping ethanol-induced deletions. 183 24

The metabolic, functional and electrical effects of ethanol were studied in the isolated isovolumic rat heart retrogradely perfused at constant flow using phosphorus-31 nuclear magnetic resonance spectroscopy and surface electrogram recordings. Ethanol (0.75 to 6.0 vol%; 128 to 1024 mM) caused a concentration-dependent decline in developed pressure without a change in adenosine triphosphate, phosphocreatine, inorganic phosphate or pH. Ethanol (6%) caused abolition of electrical activity. The functional decline could be rapidly and completely reversed by perfusing with ethanol-free solution and, significantly although not completely, reversed by increasing perfusate calcium to 4 mM. Furthermore, ethanol shifted the perfusate calcium-tetanic pressure relationship in the presence of ryanodine (1 microM) downwards and to the right. The results suggest ethanol's acute effects in this model are not mediated by changes in energy metabolism or cellular pH, but rather by sarcolemmal effects and by a decrease in both myofilament calcium sensitivity and maximal force generating ability.
J Mol Cell Cardiol 1991 Apr
PMID:Contractile, metabolic and electrophysiologic effects of ethanol in the isolated rat heart. 194 79

A library of genomic DNA fragments from Haemophilus influenzae type b (Hib) DL42 was constructed in plasmid pBR322, transformed into Escherichia coli strain RR1, and screened for recombinant clones with haemin-binding activity by plating onto haemin-containing agar. Expression of haemin-binding activity by clones correlated with the expression of a protein with an apparent molecular weight of 51,000 (51K) that was also recognized by anti-Hib strain DL42 serum in immunoblots. One recombinant clone, designated pHM2, with the smallest DNA insert (3.62 kb) was characterized further. Ethanol inhibition of expression of pHM2 in minicells revealed that the 51K protein was the result of a processing event involving a larger precursor. E. coli RR1(pHM2) adsorbed haemin in liquid suspensions as well as from solid media. Subcloning of a 2.6 kb fragment of pHM2 into a shuttle vector permitted the construction of a recombinant Hib clone, DL42(pHM1002), which overexpressed the 51K haemin-binding protein. This 51K protein appears to be peripherally associated with the inner, and possibly outer, membranes of Hib. Affinity chromatography on haemin-agarose was utilized to purify the haemin-binding protein from both E. coli RR1(pHM2) and Hib DL42(pHM1002) to near homogeneity. The use of the antibiotic globomycin in a minicell expression system and radioimmunoprecipitation analysis of Hib proteins intrinsically radiolabelled with [3H]-palmitate indicated that the 51K haemin-binding protein is a lipoprotein.
Mol Microbiol 1991 Feb
PMID:Molecular cloning, partial purification, and characterization of a haemin-binding lipoprotein from Haemophilus influenzae type b. 204 70

The effect of glucose and other monosaccharides on Giardia intestinalis was investigated by growing G. intestinalis trophozoites in Diamond's TYI-S-33 medium modified by changes in the monosaccharide component, and observing changes in the trophozoite growth and product formation (alanine, ethanol and acetate). Reducing the glucose concentration from 50 mM to 10 mM had little effect on trophozoite growth and product formation. Below 10 mM glucose, ethanol production was markedly reduced, there was a lesser effect on alanine, but acetate production was unaffected. In medium in which no glucose had been added, trophozoites grew at about half the rate of controls (50 mM glucose) and continued to form the same products. Growth in medium containing 10 mM ribose or 10 mM fructose substituted for glucose produced a metabolic profile similar to that of the no glucose added condition. The activity of a number of glycolytic and related enzymes was also determined, but the enzymic profile was not affected by the monosaccharide status of the medium. Ethanol production by trophozoites was specifically depressed by the aldehyde reductase inhibitor, valproate; 3 mM valproate reduced ethanol production by 90%. The alcohol dehydrogenase inhibitor pyrazole had no effect on ethanol production or any other parameter. This differential inhibition suggests that ethanol is produced by an aldehyde reductase or related enzyme. The observations that G. intestinalis trophozoites can continue to grow, replicate and produce the same metabolites in medium containing little or no glucose suggest that G. intestinalis is not solely dependent on glucose as a metabolic fuel.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Biochem Parasitol 1991 Mar
PMID:Glucose metabolism in Giardia intestinalis. 205 39


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