scholarly journals Regulation of phenobarbital-inducible cytochrome P-450s in rat and mouse liver following dexamethasone administration and hypophysectomy

1988 ◽  
Vol 254 (3) ◽  
pp. 789-797 ◽  
Author(s):  
R R Meehan ◽  
L M Forrester ◽  
K Stevenson ◽  
N D Hastie ◽  
A Buchmann ◽  
...  

Cytochrome P-450s are a superfamily of haem-containing proteins involved in the metabolism of foreign compounds, as well as a variety of endogenous molecules. The hepatic levels and function of this diverse group of enzymes are determined by both constitutive and xenobiotic regulators. To examine the role of constitutive factors in cytochrome P-450 regulation, the levels of three distinct groups of phenobarbital-inducible hepatic cytochrome P-450s were studied following dexamethasone-treatment or hypophysectomy. In the mouse, dexamethasone was a potent inducer of proteins within the PB1 (subfamily IIC), PB2c (family III) and PB3 (subfamily IIB) families. These findings were strikingly different from the effects in the rat where essentially no effect on PB3 expression and indeed suppression of proteins related to PB1 was observed. Determination of mRNA concentration indicated that the difference was at the level of transcription. These findings indicate that synthetic glucocorticoids have the potential to be potent phenobarbital-like inducing agents. In the mouse hypophysectomy, like dexamethasone, induced hepatic mRNA of P-450 from families P-450IIB, P-450IIC and P-450III. Again a species difference was observed as this treatment had essentially no effect in the rat. These data in the mouse indicate that factors produced in the pituitary can either affect the transcription rate of phenobarbital and dexamethasone-inducible P-450 genes or influence the stability of their mRNAs.

2021 ◽  
Vol 22 (5) ◽  
pp. 2732
Author(s):  
Nadine Reichhart ◽  
Vladimir M. Milenkovic ◽  
Christian H. Wetzel ◽  
Olaf Strauß

The anoctamin (TMEM16) family of transmembrane protein consists of ten members in vertebrates, which act as Ca2+-dependent ion channels and/or Ca2+-dependent scramblases. ANO4 which is primarily expressed in the CNS and certain endocrine glands, has been associated with various neuronal disorders. Therefore, we focused our study on prioritizing missense mutations that are assumed to alter the structure and stability of ANO4 protein. We employed a wide array of evolution and structure based in silico prediction methods to identify potentially deleterious missense mutations in the ANO4 gene. Identified pathogenic mutations were then mapped to the modeled human ANO4 structure and the effects of missense mutations were studied on the atomic level using molecular dynamics simulations. Our data show that the G80A and A500T mutations significantly alter the stability of the mutant proteins, thus providing new perspective on the role of missense mutations in ANO4 gene. Results obtained in this study may help to identify disease associated mutations which affect ANO4 protein structure and function and might facilitate future functional characterization of ANO4.


1982 ◽  
Vol 204 (1) ◽  
pp. 103-109 ◽  
Author(s):  
J F Sinclair ◽  
P R Sinclair ◽  
J F Healey ◽  
E L Smith ◽  
H L Bonkowsky

Exposure of cultured chick-embryo hepatocytes to increasing concentrations of CoCl2 in the presence of allylisopropylacetamide results in formation of cobalt protoporphyrin, with a reciprocal decrease in haem and cytochrome P-450. Treatment of rats with CoCl2 (84 mumol/kg) and 5-aminolaevulinate (0.2 mmol/kg) also results in formation of cobalt protoporphyrin and a decrease in cytochrome P-450 in the liver. Hepatic microsomal fractions from rats treated with phenobarbital, CoCl2 and 5-aminolaevulinate were analysed by polyacrylamide gel electrophoresis. Cobalt protoporphyrin was associated mainly with proteins of 50000-53000 mol.wt. The results suggest that the formation of cobalt protoporphyrin occurred at the expense of the synthesis of haem, leading to a decrease in cytochrome P-450. Furthermore, the cobalt protoporphyrin that was formed may itself have been incorporated into apocytochrome P-450.


2016 ◽  
Vol 4 (Special-Issue-October) ◽  
pp. 37-47
Author(s):  
Ana Barros ◽  
Vitoria Bell ◽  
Jorge Ferrão ◽  
Vittorio Calabrese ◽  
Tito Fernandes

Mushrooms have attracted market attention because they are a potential source of bioactive compounds able to perform several functions in organisms with benefits for the health of the consumer. Cultivation processes vary according a) industrial fermentation - in large vats to produce extracted form of mushrooms or b) closed cultivation system - individually grown in jars on an aseptic “substrate” with controlled lighting and irrigation to produce a biomass form of mushrooms. Biomass is the mycelium with primordia (young fruiting body - before the mushroom blooms) containing all the nutrients and active compounds, including β-glucans, enzymes and secondary metabolites. The classification of mushroom biomass varies according to the presentation; the biomass can be classified as a “food” if in powder form or, classified as a “dietary supplement” in tablet form. While tablet mushroom biomass is considered a dietary supplement, mushroom extracts are designated pharmaceutical compounds, pharmanutrients or nutraceuticals. Here we illustrate the difference between mushrooms in the biomass and extract forms, the similarities and differences on its content on enzymes, secondary metabolites and on β-glucans, as a soluble and fermentable fibre. Of particular note is the rich enzyme activity in the biomass form of mushrooms. Such activity includes enzymes that prevent oxidative stress (superoxide dismutase), enzymes that prevent cellular growth (protease, glucoamylase) and enzymes that promote detoxification (cytochrome P-450, peroxidase, glucose-2-oxidase). β-glucans have been proposed to act as “biological response modifiers” based on their effects on the immune system, and its role in the prevention and treatment of various metabolic syndrome-linked diseases. This review focuses also on some described health-promoting potential of mushroom biomass, all through immunomodulation. The role of intestinal microbiota is enhanced.


2018 ◽  
Vol 28 (55) ◽  
pp. 845-862
Author(s):  
Fabiana Barros Medeiros ◽  
Francieli Sant'ana Marcatto ◽  
Hélio Silveira ◽  
MariaTeresa De Nóbrega

Esta pesquisa tem como objetivo estudar a vulnerabilidade à erosão dos solos da zona de contato do arenito da Formação Caiuá com o basalto da Formação Serra Geral, no município de Araruna, Mesorregião Noroeste Paranaense, dando enfoque ao papel da estabilidade da estrutura atual dos solos, considerando-se as alterações produzidas pelas formas de uso e ocupação da área. A análise realizada também considerou as variações das características morfológicas dos solos em perfil e ao longo da litossequência (sistema pedológico), assim como os seus reflexos na geração de setores mais ou menos suscetíveis à erosão na vertente. Para o levantamento dos solos ao longo da vertente foram utilizados os procediments propostos pela Análise Estrutural da Cobertura Pedológica e a coleta de amostras para a determinação da granulometria e estabilidade de agregados. Os resultados indicaram a ação dos fluxos de água laterais e verticais, atuando na transformação dos horizontes dos solos ao longo da vertente e uma variação da estabilidade estrutural associada as características morfológicas dos solos e ao tipo de uso e manejo empregado. Os Argissolos apresentaram agregados pequenos e um gradiente textural entre o horizonte superficial e subsuperficial, lhe conferindo uma forte suscetibilidade a erosão. O Nitossolo não apresentou grande diferenciação no tamanho dos agregados, exceto no horizonte Bw, onde a redução no tamanho dos agregados se associaram a mudança morfológica da estrutura do solo.AbstractThis research aims to study the vulnerability to soil erosion of the contact zone of the sandstone Formation Caiuá with basalt of the Serra Geral Formation, in the municipality of Araruna, Paraná Northwest Region, giving focus to the role of the stability of the current structure of soils, considering the changes produced by the forms of use and occupation of the area. The analysis also considered variations of morphological characteristics of soils in profile and along the lithosactivity (pedological system), as well as your reflexes in the generation of sectors more or less susceptible to erosion in the shed. For the survey of the soils along the strand, the procedures proposed by the Structural Analysis of the Pedological Coverage and the collection of samples for the determination of the granulometry and stability of aggregates were used. The results indicated the action of the lateral and vertical water flows, acting on the transformation of the soil horizons along the slope and a variation of the structural stability associated with the morphological characteristics of the soils and the type of use and management used. The Argisols presented small aggregates and a textural gradient between the surface and subsurface horizon, giving it a strong susceptibility to erosion. The Nitossolo did not show great differentiation in the size of the aggregates, except in the Bw horizon, where the reduction in the size of the aggregates was associated to the morphological change of the soil structure.Keywords: structural analysis of the soil cover, stability of aggregates, susceptibility to erosion, pedological systems.


2019 ◽  
Vol 5 (8) ◽  
pp. eaax1031 ◽  
Author(s):  
Lei Bai ◽  
Jiazhen Dong ◽  
Zhenqiu Liu ◽  
Youliang Rao ◽  
Pinghui Feng ◽  
...  

Helicases play pivotal roles in fundamental biological processes, and posttranslational modifications regulate the localization, function, and stability of helicases. Here, we report that methionine oxidation of representative helicases, including DNA and RNA helicases of viral (ORF44 of KSHV) and cellular (MCM7 and RIG-I) origin, promotes their expression and functions. Cellular viperin, a major antiviral interferon-stimulated gene whose functions beyond host defense remain largely unknown, catalyzes the methionine oxidation of these helicases. Moreover, biochemical studies entailing loss-of-function mutations of helicases and a pharmacological inhibitor interfering with lipid metabolism and, hence, decreasing viperin activity indicate that methionine oxidation potently increases the stability and enzyme activity of these helicases that are critical for DNA replication and immune activation. Our work uncovers a pivotal role of viperin in catalyzing the methionine oxidation of helicases that are implicated in diverse fundamental biological processes.


1940 ◽  
Vol 30 (4) ◽  
pp. 622-638 ◽  
Author(s):  
S. K. Kon ◽  
S. Y. Thompson

1. The influence of storage in the light and in the dark at ordinary temperature and in a heated room at 70–80° F. on the carotene content of finely ground artificially dried grass stored in paper sacks and jute sacks was studied. There was an initial drop in carotene content from 61·1 to 46·5 mg./100 g., i.e. 23·9%, in the first month, and a total loss of 31·4% during 6 months' storage (August to February). No difference could be detected either between treatments or types of containers.2. There was a marked loss of carotene during 13 months' storage of baled artificially dried grass and of hays, amounting to 30–40% of the original value.3. Two methods of estimating carotene were compared. The method of Ferguson & Bishop (1936) gave higher results than the method of Peterson, Hughes & Freéman (1937). The difference is probably due to incomplete extraction in the latter method.4. Chromatographic analyses of “carotene” fractions from the above grasses showed the presence of coloured impurities amounting to 20·5–33·8% of the total recovered pigments.5. As these impurities are biologically inactive, chromatographic analysis or the use of special solvents are probably necessary for the accurate determination of carotene in forage.


1982 ◽  
Vol 203 (1) ◽  
pp. 161-168 ◽  
Author(s):  
G. Gordon Gibson ◽  
Terry C. Orton ◽  
Paul P. Tamburini

Hypolipidaemic drugs induce peroxisomal proliferation in the liver and many induce the formation of the hepatic endoplasmic reticulum in general and the formation of cytochrome P-450 in particular. We have induced the formation of rat liver microsomal cytochrome P-450 by the administration of the hypolipidaemic drug clofibrate, isolated the endoplasmic reticulum, solubilized the cytochrome P-450 from these membranes and subdivided the cytochrome P-450 into four fractions by the use of hydrophobic, anionic, cationic and adsorption chromatography. One of these fractions (cytochrome P-450 fraction 1) was highly purified to a specific content of 17nmol of cytochrome P-450/mg of protein and the protein was active in a reconstituted enzyme system towards the 12- and 11-hydroxylation of the fatty acid, dodecanoic (lauric) acid, with preferential activity towards the 12-hydroxy metabolite. This reconstituted activity was absolutely dependent on NADPH, NADPH-cytochrome P-450 reductase and cytochrome P-450, indicating the role of the mixed-function oxidase system in the metabolism of lauric acid. Another fraction of the haemoprotein (cytochrome P-450 fraction 2) preferentially formed 11-hydroxylauric acid, whereas a third fraction (cytochrome P-450 fraction 3) exhibited only trace laurate oxidase activity and was similar to the phenobarbitone form of the haemoprotein in that these last two cytochromes rapidly turned-over the drug benzphetamine. The molecular weights and spectral properties of these cytochrome P-450 fractions are reported, along with the phenobarbitone-induced form of the enzyme and the nature of the cytochrome(s) induced by clofibrate pretreatment are discussed in the terms of possible haemoprotein heterogeneity.


2006 ◽  
Vol 34 (5) ◽  
pp. 601-629 ◽  
Author(s):  
Robin K. Henson

Effect sizes are critical to result interpretation and synthesis across studies. Although statistical significance testing has historically dominated the determination of result importance, modern views emphasize the role of effect sizes and confidence intervals. This article accessibly discusses how to calculate and interpret the effect sizes that counseling psychologists use most frequently. To provide context, the author presents a brief history of statistical significance tests. Second, the author discusses the difference between statistical, practical, and clinical significance. Third, the author reviews and graphically demonstrates two common types of effect sizes, commenting on multivariate and corrected effect sizes. Fourth, the author emphasizes meta-analytic thinking and the potential role of confidence intervals around effect sizes. Finally, the author gives a hypothetical example of how to report and potentially interpret some effect sizes.


1988 ◽  
Vol 253 (2) ◽  
pp. 569-576 ◽  
Author(s):  
C J Reed ◽  
E A Lock ◽  
F De Matteis

1. The olfactory epithelium of male hamsters has been found to be extremely active in the cumene hydroperoxide-supported oxidation of tetramethylphenylenediamine, and this peroxidase activity has been shown to be cytochrome P-450-dependent. 2. The interaction of a series of suicide substrates of cytochrome P-450 with the hepatic and olfactory mono-oxygenase systems has been assessed by determination of peroxidase, 7-ethoxycoumarin O-de-ethylase (ECOD) and 7-ethoxyresorufin O-de-ethylase (EROD) activities after treatment in vivo with these compounds. Chloramphenicol, OOS-trimethylphosphorothiolate and two dihydropyridines [DDC (3,5-diethoxycarbonyl-1,4-dihydrocollidine) and 4-ethyl DDC (3,5-diethoxycarbonyl-4-ethyl-1,4-dihydro-2,6-dimethylpyridine)] all caused similar percentage inhibitions of hepatic and olfactory activities, but the absolute amounts of enzymic activity lost were considerably greater in the latter tissue. In contrast, halothane had little effect upon hepatic cytochrome P-450-dependent reactions, whereas it severely inhibited those of the olfactory epithelium. 3. The time course of loss and recovery of hepatic and olfactory peroxidase, ECOD and EROD activities after a single dose of 4-ethyl DDC was studied. The rates of loss of activity observed were very similar, irrespective of tissue or reaction examined. In the olfactory epithelium, all three activities recovered concurrently and at a rate similar to that of the hepatic peroxidase activity. In contrast, the hepatic de-ethylation of 7-ethoxycoumarin and 7-ethoxy-resorufin recovered significantly more rapidly. 4. It is suggested that this behaviour is due to 4-ethyl DDC acting not only as a suicidal inhibitor but also as an inducer of certain forms of cytochrome P-450 in the liver; in the olfactory epithelium, however, inactivation, but not induction, occurs. Classical inducing agents were reported to have no effect upon olfactory cytochrome P-450, and in the present study neither phenobarbitone nor beta-naphthoflavone treatment had any effect upon olfactory cytochrome P-450-dependent reactions, although it induced those of the liver.


2017 ◽  
Vol 12 (6) ◽  
pp. 636-640 ◽  
Author(s):  
Adam Piechna ◽  
Leszek Lombarski ◽  
Bogdan Ciszek ◽  
Krzysztof Cieslicki

Background Intracranial arterial dissections might be attributed to the particular biomechanical properties of their specific layers. Also, knowledge of adventitia properties would be crucial in the context of intracranial balloon angioplasty. Aims The purpose of this work was to determine the rupture pressure of separated adventitia and compare it to intact cerebral arterial segments. Methods Brain specimens were harvested from 14 autopsy subjects (age range from 23 to 86 years). Pressure-inflation tests were conducted on proximal segments of middle cerebral arteries and separated adventitia layers from contralateral arteries to assess the rupture pressure values. Results The averaged rupture pressure of adventitia layers was 1.41 SD 0.25 atm (1072 SD 190 mmHg), whereas for intact arterial segments it was 2.32 SD 0.70 atm (1763 SD 532 mmHg) and diminished with age according to nonlinear regression trends. The difference beetween the aformentioned rupture pressures was positively correlated with rupture pressure of intact arterial segments ( R2 = 0.88; p < 0.001). Conclusions The obtained experimental results indicate a leading role of adventitia in building arterial strength under supraphysiological pressure conditions. The greater the rupture pressure of complete cerebral arteries, the smaller the contribution of adventitia in overall wall resistance.


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