Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ethanol-inducible cytochrome P450 (CYP) 2E1 (CYP2E1) is responsible for the metabolism of many xenobiotics which exert toxic effects in humans. Specific inhibitors might constitute valuable tools in the elucidation of the pharmacological and toxicological roles of this isozyme in vivo. In the present investigation we have evaluated the effects of a drug used for treatment of ethanol withdrawal states, chloromethiazole (CMZ), on CYP2E1 expression in rat liver. A 4-fold induction of CYP2E1 was observed after 3 days of starvation, accompanied by a similar increase in the level of the corresponding mRNA. CMZ specifically inhibited the elevation of CYP2E1 mRNA and protein, but did not prevent CYP2B1 and CYP3A1 or CYP1A1 induction caused by treatment with phenobarbital or beta-naphthoflavone, respectively. From nuclear run-off experiments it was apparent that the rate of the CYP2E1 gene transcription was inhibited greatly by CMZ treatment. Rats treated with ethanol in a total enteral nutrition model had higher CYP2E1-dependent hepatic microsomal activities of p-nitrophenol hydroxylase and carbon tetrachloride-induced lipid peroxidation than controls, and simultaneous CMZ treatment abolished the ethanol-dependent induction. In vitro experiments with rat liver microsomes showed that CMZ did not act as an inhibitor of CYP2E1-dependent catalytic activities or as an inhibitor of microsomal NADPH and CYP2E1-dependent lipid peroxidation. In conclusion, we suggest that CMZ might constitute an efficient and specific inhibitor of CYP2E1 expression suitable for in vivo experiments.
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PMID:Chlormethiazole as an efficient inhibitor of cytochrome P450 2E1 expression in rat liver. 801 72

we isolated a novel gene that is selectively induced both in roots and shoots in response to sulfur starvation. This gene encodes a cytosolic, monomeric protein of 33 kD that selectively binds NADPH. The predicted polypeptide is highly homologous ( > 70%) to leguminous isoflavone reductases (IFRs), but the maize protein (IRL for isoflavone reductase-like) belongs to a novel family of proteins present in a variety of plants. Anti-IRL antibodies specifically recognize IFR polypeptides, yet the maize protein is unable to use various isoflavonoids as substrates. IRL expression is correlated closely to glutathione availability: it is persistently induced in seedlings whose glutathione content is about fourfold lower than controls, and it is down-regulated rapidly when control levels of glutathione are restored. This glutathione-dependent regulation indicates that maize IRL may play a crucial role in the establishment of a thiol-independent response to oxidative stress under glutathione shortage conditions.
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PMID:A maize gene encoding an NADPH binding enzyme highly homologous to isoflavone reductases is activated in response to sulfur starvation. 859 60

There is evidence to suggest that the mechanism of antioxidant effect of prostaglandin E1 (PGE1) is due to decrease of radical species generation by cytochrome P-450 in rat liver microsomes. Chronic alcohol intoxication increased NADPH oxidation, cytochrome P-450 content and NADPH-stimulated chemoluminiscence of microsomes. Ethanol also raised superoxide dismutase (SOD) activity in microsomes. PGE1 decreased cytochrome P-450 content, normalized NADPH oxidation, NADPH-induced chemoluminiscence and SOD activity in the liver of alcohol-treated rats. PGE developed the similar effect after microsomal induction by both acetone combined with starvation and phenobarbital normalizing all the above parameters. Therefore, PGE1 affects on both, ethanol-inducible IIE1 and phenobarbital-inducible IIB1 isoforms.
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PMID:Cytochrome P-450 and free radical generation in rat liver microsomes under the influence of prostaglandin E1. 887 71

Hepatocytes isolated from fed female rats are characterized by the lower contents of cytochrome P-450 and more slowly metabolize the xenobiotic p-nitroanisole (p-NA) than hepatocytes from males. The starvation does not change the cytochrome P-450 contents, but depresses the p-NA biotransformation. The inhibition of p-NA O-demethylation capacity is a result of insufficiently reduced equivalent supply, because the addition of exogenous NADPH to the cells with digitonin-permeabilized plasma membrane increases p-nitrophenol (p-NPh) formation. In the presence of exogenous NADPH hepatocytes from fasting male and female rats produce more p-NPh, than those from fed ones. That suggests the induction of xenobiotic biotransformation system during starvation. Sex differences in response of xenobiotic biotransformation system to starvation manifest themselves in different ratio in contents of free and conjugated p-NPh.
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PMID:[Effect of starvation on the metabolism of the xenobiotic p-nitroanisole in isolated hepatocytes of rats of both sexes]. 950 76

We studied the effect of prostaglandin F2 alpha on parameters related to microsomal metabolism (free radical production and lipid peroxidation, glutathione content and activity of microsomal oxidases) after an induction by ethanol or acetone combined with starvation. Long-term ethanol administration led to a significant increase in lipid peroxide formation and NADPH-dependent chemiluminescence amplified by luminol and lucigenin. At the same time hydrogen peroxide production and NADPH-stimulated lipid peroxidation were enhanced although the effect did not reach the level of statistical significance. The concentration of reduced glutathione (GSH) in the liver was decreased 2-fold, whereas oxidized glutathione (GSSG) content remained unaltered. Ethanol intoxication resulted in an increase in 7-ethoxycoumarin-O-deethylase (ECOD), 7-benzyloxycoumarin-O-deethylase (BCOD) and 7-ethoxy-resorufin-O-deethylase (EROD) activities, whereas 7-pentoxyresorufin-O-deethylase (PROD) and ethylmorphin-N-demethylase (EMND) activities were unaltered. The combination of acetone treatment with starvation resulted in a significant increase in lipid and hydrogen peroxide formation, NADPH-dependent lipid peroxidation and chemiluminescence. GSH and GSSG concentration in the liver dramatically decreased 5- and 3-fold, respectively. The acetone treatment led to significant increase in EROD, ECOD, BCOD, PROD and EMND activities. The treatment of ethanol-intoxicated rats with prostaglandin F2 alpha (PGF2 alpha) exerted more pronounced prooxidant effect on liver than action of alcohol itself. At the same time, PGF2 alpha improved most of parameters changed by acetone treatment combined with starvation, decreasing lipid peroxide and radical formation and enhancing GSH and GSSG contents.
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PMID:Effect of prostaglandin F2 alpha on free radical generation, glutathione content and microsomal oxidase activities in rat liver microsomes induced either by ethanol or acetone. 956 47

Herein we report on the kinetic and protein expression of glucose-6-phosphate dehydrogenase (G6PDH), 6-phosphogluconate dehydrogenase, and malic enzyme (ME) in the liver of the trout (Oncorhynchus mykiss) during a long-term starvation-refeeding cycle. Starvation significantly depressed the activity of these enzymes by almost 60%, without changing the Michaelis constant. The time response to this nutritional stimulus increased with fish weight. The sharp decline in G6PDH and ME activities was due to a specific protein-repression phenomenon, as demonstrated by molecular and immunohistochemical analyses. Also, the dimeric banding pattern of liver G6PDH shifted from the fully reduced and partially oxidized forms, predominant in control, to a fully oxidized form, more sensitive to proteolytic inactivation. Refeeding caused opposite effects in both protein concentration and enzyme activities of about twice the control values in the first stages, later reaching the normal enzyme activity levels. Additionally, the partially oxidized form of G6PDH increased. The kinetics of these enzymes were examined in relation to the various metabolic roles of NADPH. These results clearly indicate that trout liver undergoes protein repression-induction processes under these two contrasting nutritional conditions.
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PMID:Impact of starvation-refeeding on kinetics and protein expression of trout liver NADPH-production systems. 960 11

Hansenula polymorpha (syn. Pichia angusta) is able to grow on nitrate as sole nitrogen source. Nitrate reductase (NR) assays, optimized in crude extracts from nitrate-grown cells, revealed that NR preferentially used NADPH, but also used NADH, as electron donor and required FAD for maximum activity. NR activity was present in nitrate-grown and nitrite-grown cells, and was absent in cells grown in ammonium, glutamate and methylamine. Addition of reduced nitrogen compounds to nitrate-grown cells led to loss of NR activity, even if added with nitrate. Under nitrogen starvation, NR activity was not observed; however, following growth on nitrate, NR activity is maintained in the absence of nitrate. Increases but not decreases in NR activity were dependent on protein synthesis. Conditions for chlorate selection were optimized, and Nit- (nitrate-) mutants were isolated. Some of these mutants showed reduced or absent NR activity. Sixty-one NR- mutants revealed the monogenic recessive nature of their lesions and were grouped in 10 complementation classes. These mutants will be used in gene cloning experiments aimed at identifying structural and regulatory elements involved in the first step of nitrate reduction.
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PMID:Nitrate reduction and the isolation of Nit- mutants in Hansenula polymorpha. 972 55

The metabolism of carbohydrates is largely determined by their chemical properties. Glucose may have been selected, over the other aldohexoses, because of its low propensity for glycation of proteins. That carbohydrate is stored in polymeric form (glycogen) is dictated by osmotic pressure considerations. That stored fat is about eight times more calorically dense than glycogen, when attendant water is factored in, accounts for the predominance of fat as a storage form of calories and, also, for the fact that ingested carbohydrate is oxidized promptly (that is, fuel of the fed state) rather than being extensively stored. That stored glycogen is accompanied by so much water accounts for the fact that the brain only has very small glycogen stores. Carbohydrate has two important advantages, over fat, as a metabolic fuel; it is the only fuel that can produce ATP in the absence of oxygen, and more ATP is produced per O2 consumed when glucose is oxidized, compared with when fat is oxidized. These advantages probably determine the preference of many cell types for carbohydrate. In addition to its use as a metabolic fuel, glucose plays other important roles such as provision of NADPH via the pentose phosphate pathway, and as a source material for the synthesis of other key carbohydrates, for example, ribose and deoxyribose for nucleic acid synthesis and substrates for the synthesis of glycoproteins, glycolipids and glycosaminoglycans. It can also play a key role in anaplerosis. Although it is widely acknowledged that gluconeogenesis plays a crucial role in starvation it is now apparent that prandial gluconeogenesis occurs, both in the metabolic disposal of dietary amino acids and in the synthesis of glycogen by the indirect pathway. Although there is, strictly speaking, no dietary requirement for carbohydrate it is evident that glucose is a universal fuel for probably all cells in the body and carbohydrate is the cheapest source of calories and the major source of dietary fibre. These observations, together with the fact that glucose is the preferred metabolic fuel for the brain, permit us to recommend appreciable quantities of carbohydrate in all prudent diets.
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PMID:Comments on metabolic needs for glucose and the role of gluconeogenesis. 1036 87

The screening of liver and heart cDNA libraries from the teleost Fundulus heteroclitus with degenerate oligonucleotide probes to conserved alpha-helical regions in mammalian P450s resulted in the identification of two cDNAs that together represent a novel P450 subfamily, the CYP2Ns. Northern analysis demonstrated that CYP2N1 transcripts are most abundant in liver and intestine, whereas CYP2N2 mRNAs are most abundant in heart and brain. CYP2N1 and CYP2N2 proteins were co-expressed with NADPH-cytochrome P450 oxidoreductase in Sf9 insect cells, and their ability to metabolize arachidonic acid and xenobiotic substrates was examined. Both CYP2N1 and CYP2N2 metabolize arachidonic acid to epoxyeicosatrienoic acids. Epoxidation is highly regio- and enantioselective with preferential formation of (8R,9S)-epoxyeicosatrienoic acid (optical purities are 91 and 90% for CYP2N1 and CYP2N2, respectively) and (11R, 12S)-epoxyeicosatrienoic acid (optical purities are 92 and 70% for CYP2N1 and CYP2N2, respectively). CYP2N1 and CYP2N2 also catalyze the formation of a variety of hydroxyeicosatetraenoic acids. Both P450s have benzphetamine N-demethylase activities but show minimal alkoxyresorufin O-dealkylase activities. To investigate factors affecting CYP2N expression in vivo, CYP2N transcripts were examined following starvation and/or treatment with 12-O-tetradecanoyl phorbol-13-acetate. Intestinal CYP2N1 mRNAs decrease in starved and/or phorbol ester-treated fish, whereas intestinal CYP2N2 transcripts decrease only following phorbol ester treatment. Interestingly, cardiac CYP2N2 expression decreases following phorbol ester treatment but increases following starvation. These results demonstrate that members of this novel P450 subfamily encode early vertebrate forms of arachidonic acid catalysts that are widely expressed and are regulated by environmental factors. Given the wealth of information on the functional role of P450-derived arachidonate metabolites in mammals, we postulate that CYP2N1 and CYP2N2 products have similar biological functions in early vertebrates. The identity of the mammalian orthologue(s) of the CYP2Ns remains unknown.
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PMID:Identification, functional characterization, and regulation of a new cytochrome P450 subfamily, the CYP2Ns. 1064 80

In the C(4) plant maize (Zea mays L.), two ferredoxin isoproteins, Fd I and Fd II, are expressed specifically in mesophyll and bundle-sheath cells, respectively. cDNAs for these ferredoxins were introduced separately into the cyanobacterium Plectonema boryanum with a disrupted endogenous ferredoxin gene, yielding TM202 and KM2-9 strains expressing Fd I and Fd II. The growth of TM202 was retarded under high light (130 micromol/m(2)/s), whereas KM2-9 grew at a normal rate but exhibited a nitrogen-deficient phenotype. Measurement of photosynthetic O(2) evolution revealed that the reducing power was not efficiently partitioned into nitrogen assimilation in KM2-9. After starvation of the cells in darkness, the P700 oxidation level under far-red illumination increased significantly in TM202. However, it remained low in KM2-9, indicating an active cyclic electron flow. In accordance with this, the cellular ratio of ATP/ADP increased and that of NADPH/NADP(+) decreased in KM2-9 as compared with TM202. These results demonstrated that the two cell type-specific ferredoxins differentially modulate electron flow around photosystem I.
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PMID:Differential electron flow around photosystem I by two C(4)-photosynthetic-cell-specific ferredoxins. 1101 7


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