Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Enzyme Induction”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,423 records · Page 79Linked to original sources
PubMed1992

Divergent effects of different enzyme-inducing agents on endogenous and exogenous testosterone.

The effects of three different enzyme-inducing drugs (antipyrine 1200 mg, phenobarbital 100 mg, rifampicin 600 mg per day for 7 days) on plasma and urinary testosterone concentrations, plasma gonadotropin levels, antipyrine kinetics, and urinary 6 beta-hydroxycortisol excretion were studied in 18 healthy volunteers. Changes in plasma and urinary testosterone concentrations following exogenous testosterone undecanoate (TU) were also investigated. Although both antipyrine and rifampicin increased antipyrine clearance by about 60%, they produced contrary effects on testosterone: antipyrine lowered the total morning plasma testosterone and plasma testosterone AUC following TU, while rifampicin led to increases of about 20% and 78%, respectively. By contrast, phenobarbital did not significantly alter the endogenous and exogenous plasma testosterone concentrations, but it increased the urinary excretion of testosterone by more than 60%. The other two enzyme inducers did not alter this parameter. Gonadotropin levels remained unchanged. The results indicate that different enzyme-inducing agents exert divergent effects on endogenous and exogenous testosterone concentrations and suggest that the effect of enzyme induction on endogenous testosterone depends on the type of microsomal enzyme-inducing drug used rather than on the extent of the induction achieved.

Adult↗
PubMed1999

Induction of cytochrome-P450 in cryopreserved rat and human hepatocytes.

Our laboratory has been routinely using suspended and cultured human hepatocytes for predicting drug metabolism and enzyme induction by drug candidates to aid drug discovery. Increasing limitation and irregular availability of human tissue has indicated the need for maximizing the use of this valuable resource. Cryopreservation of surplus hepatocytes after isolation would greatly increase the potential of this model. However, cryopreservation of hepatocytes by various methods has resulted in cells with poor metabolic activity and unacceptably low survival rates in culture. Recently, Zaleski et al. (Biochem. Pharmacol. 46 (1993) 111-116) reported that cryopreserved rat hepatocytes retained metabolic capacity similar to fresh hepatocytes when the cells were preincubated for 30 min at 37 degrees C in Krebs Ringer bicarbonate buffer prior to freezing. To further explore this methodology, both the functional capacity of the cells in culture as well as their ability to retain CYP inducibility were investigated with thawed cryopreserved hepatocytes. Although human hepatocytes were used in this study the initial work focused on rat hepatocytes as a cell model. Our results showed that while the preincubation step did not appear to effect the initial viability of cryopreserved hepatocytes, survival of the cells in culture was greatly enhanced. Plating efficiencies for nonpreincubated cryopreserved hepatocytes were decreased to approximately 15% of fresh cells after 48 h in culture. In contrast, cells that had been preincubated prior to freezing had an excellent plating efficiency (approximately 60%) and responded to classical CYP inducers dexamethasone, beta-naphthoflavone and phenobarbital in a manner indistinguishable from that of fresh hepatocytes. Experiments with human hepatocytes have also demonstrated similar results. This is the first time to our knowledge that cryopreserved hepatocytes from both rat and human have been shown to reproducibly respond to CYP inducers in culture.

Animals↗
PubMed1984

Gamma-glutamyltranspeptidase induction by cortisol in liver parenchyma of unweaned rats.

In contrast to many differentiated hepatic functions developing after birth, very little is known about in vivo glucocorticoid influences on postnatal expression of fetal liver enzymes, such as GGT. This study showed that cortisol markedly induces liver GGT activity in unweaned rats, but has no effect after weaning. Enzyme induction was dose- and time-dependent and occurred in parenchymal cells, progressing with time from zone 1 to zone 2 of the liver acinus. Zone-3 hepatocytes were unresponsive even after a 5-day treatment. Lag-times for GGT induction in zones 1 and 2 of the liver acinus were 1 to 2 days and 2 to 3 days, respectively. From this, a permissive cell change, determined by the hormone administration itself, seems required for the hepatocyte GGT induction by cortisol in pre-weaning rats.

Animals↗
PubMed2001

Phytochemicals from cruciferous plants protect against cancer by modulating carcinogen metabolism.

Several epidemiologic studies suggest that consumption of cruciferous vegetables may be particularly effective (compared with total fruit and vegetable consumption) in reducing cancer risk at several organ sites. Crucifers that are widely consumed are especially rich in glucosinolates, which are converted by plant myrosinase and gastrointestinal microflora to isothiocyanates. A number of isothiocyanates and a limited number of glucosinolates that were examined effectively block chemical carcinogenesis in animal models. Many isothiocyanates are also potent inducers of phase 2 proteins. Substantial evidence supports the view that phase 2 enzyme induction is a highly effective strategy for reducing susceptibility to carcinogens. This conclusion has recently received strong molecular support from experiments on mice in which the specific transcription factor, nrf2, which is essential for induction of phase 2 proteins, was deleted. In these knock-out mice, the basal levels of phase 2 enzymes are very low and not inducible. Accordingly, these mice are much more susceptible than their wild-type counterparts to benzo[a]pyrene forestomach carcinogenesis and are not protected by phase 2 inducers. These experiments provide very strong evidence for a major role of phase 2 enzymes in controlling the risk of exposure to carcinogens. An increasing number of phase 2 proteins that exert a variety of protective mechanisms are being identified. Thus, in addition to detoxifying electrophiles, these proteins exercise versatile, long-lasting and catalytic antioxidant protection.

Animals↗
PubMed1975

[The virulence of erysipelothrix rhusiopathiae strains and their neuraminidase production (author's transl)].

We studied the virulence of 20 Erysipelothrix rhusiopathiae strains in albino mice and investigated the interdependence between virulence, growth rate, and neuraminidase production. The minimal number of germs, lethal to mice (LD100) varied among the strains between 10(1) and mor ethan 10(7) per animal. The course of the disease was also very different. Some strains killed the mice rapidly within 3 days. In other strains, however, even a very high number of bacteria caused death only 7 days after infection or later, in which cases the disease became manifest long in advance by ruffled fur and glutinous eyes. A significant correlation was found between the average neuraminidase production in different media and the virulence (p equal to 99%; Fig. 2). We found a less marked dependence between growth rate and virulence (Fig. 3). Neuraminidase activity and growth rate seem to influence virulence rather independently. This is concluded from the fact, that some virulent strains are characterized by quick growth and by producing either no neuraminidase or in small quantities only. On the other hand, neuraminidase production cannot be separated completely from growth rate. An induction of neuraminidas activity in vivo was not observed, even when the bacteria persisted in the mice over a long period of time. We therefore conclude that a short term enzyme induction is not probable.

Enzyme Induction↗
PubMed1996

Cytochromes P450 5: induction of cytochrome P4501A1: a model for analyzing mammalian gene transcription.

The induction of microsomal cytochrome P4501A1 by polycyclic aromatic hydrocarbons represents an interesting response by which mammalian cells adapt to xenobiotic exposure. Enzyme induction reflects increased transcription of the corresponding CYP1A1 gene. Analyses of the induction mechanism using genetic, biochemical, and molecular biological approaches have revealed a novel transcriptional regulatory pathway that involves ligand-dependent heterodimerization between two basic helix-loop-helix proteins (the Ah receptor and Arnt), interaction of the heterodimer with a xenobiotic-responsive enhancer, transmission of the induction signal from the enhancer to the CYP1A1 promoter, and alterations in chromatin structure. Current techniques permit examination of the induction mechanism in intact cells and analyses of the CYP1A1 gene in its native chromosomal configuration. Such experiments generate new insights into the control of mammalian transcription that are of relatively broad interest.

Animals↗
PubMed1985

Precocious induction of tryptophan dioxygenase by glucocorticoid in suckling rats and correlation with change in glucocorticoid receptor.

When young rats (less than 14 days old) were treated once a day for 2 days with 100 micrograms/100 g body weight of dexamethasone, their liver cytosol showed a sharp new peak of glucocorticoid binding protein (peak C) eluted with 0.14 M NaCl on DEAE-cellulose chromatography. When the young rats were given a single injection of the hormone, the chromatogram showed a dominant peak of binding protein (peak B), eluted with 0.07 M NaCl, which was similar to that in untreated rats. The appearance of peak C on two treatments of young rats with hormone was confirmed by both in vivo and in vitro labeling and also studies on the nuclear fraction. Peaks B and C were specific hormone-binding proteins as shown with excess unlabeled hormone. The appearance of peak C was concomitant with the precocious induction of tryptophan dioxygenase in the liver of the young rats, and pretreatment with two injections of dexamethasone were necessary for maximal enzyme induction. On the other hand, in adult rats a single injection of dexamethasone (of 20 micrograms/100 g body weight or more) was enough to cause the appearance of peak C and induce tryptophan dioxygenase activity maximally; an additional injection of the hormone did not change the chromatographic pattern of the specific binding or the enzyme activity. For this effect in young rats, dexamethasone could not be replaced by other hormones such as glucagon, growth hormone, thyroid hormones, insulin, sex steroids or short-acting glucocorticoid.

Aging↗
PubMed2004

Chemoprevention by isothiocyanates and their underlying molecular signaling mechanisms.

Chemoprevention is a cancer preventive strategy to inhibit, delay or reverse carcinogenesis using naturally occurring or synthetic chemical agents. Numerous epidemiological studies as well as experimental animal studies clearly demonstrate that high intake of cruciferous vegetables protects against tumorigenesis. Thus, cruciferous vegetables have been of great interest for potential use in the chemoprevention of cancer. Cruciferous vegetables are rich source of glucosinolates, which are degraded into isothiocyanates by enzymatic action of plant-specific myrosinase or intestinal flora in the body. It appears that significant portion of the chemopreventive effects of isothiocyanates may be associated with the inhibition of the metabolic activation of carcinogens by cytochrome P450s (Phase I), coupled with strong induction of Phase II detoxifying and cellular defensive enzymes. Inductions of Phase II cellular enzymes are largely mediated by the antioxidant responsive element (ARE), which is regulated by the transcriptional factor, Nrf2. Additional potent regulatory mechanisms of Nrf2 include the different signaling kinase pathways (MAPK, PI3K, PKC and PERK) as well as other non-kinase dependent mechanisms. Moreover, apoptosis and cell cycle perturbations appear to be yet another potential chemopreventive mechanisms elicited by isothiocyanates, especially with respect to the effects on pre-initiated or initiated tumor cells. Finally, modulation of other critical signaling mediators, including the NF-kappaB and AP-1 by a wide array of chemopreventive agents including isothiocyanates may also contribute to the overall chemopreventive mechanisms.

Animals↗
PubMed2001

Estrogen-dependent activity of kidney lysosomal proteolytic enzymes.

Drug-induced kidney injury is a potential complication of a number of medicaments. The wide-spread use of estrogens in the form of oral contraceptives and in the form of hormonal replacement therapy, has necessitated extensive studies on the biochemical alterations. The following effects of estrogens on kidney are discussed in greater detail with special regard to enzyme induction. The aim of the study was to evaluate the influence of long-term activity estrogens on kidney lysosomal enzymes like cathepsin B, D and L. Female rats were divided randomly into eight experimental groups. Oestradiolum benzoicum was used for the purpose of this study. Estrogens were given i.m. one time per week for 8 weeks in different doses, respectively: E1--0.00075 g/kg b.w., one time per week; E1.1--0.00075 g/kg b.w. every three days; E2--0.0015 g/kg b.w.. one time per week. E2.1--0.0015 g/kg b.w.. every three days; E3--0.03 g/kg b.w.. one time per week; E3.1--0.003 g/kg b.w.. every three days; KO--untreated animals; K1--treated control, rats received oleum pro injection at the dose of 1.2 ml/100 g b.w. The activity of free and bound fractions of lysosomal enzymes, such as cathepsin B, D and L were assayed in kidney homogenates using spectrophotometric methods. Differences between various experimental groups were tested with ANOVA test. The activity of cathepsin B, D and L fractions showed significant changes compared to control groups. The observed changes were not characteristic in all the studied groups. The most important changes referred to the activity of cathepsin B and D. Differences were noted between the enzymes activity in animals treated with the smallest dose of estrogen and that in control groups. It was smaller in group E1 than in groups K0 and K1. The activity of cathepsin B was higher in group E1 than in control groups. There was no correlation between the dose of injected estrogens and the observed lysosomal activity changes. The changes in lysosomal activity were uncharacteristic.

Animals↗
PubMed1982

[Polyenzymatic activation of cellular hydrolases induced by interferon; its role in cytolysis and other cellular manifestations induced by interferon].

Interferon (IFN) treatment of human effector T cells activates CMC directed against K562 targets. An increase of the activity of the different hydrolytic enzymes tested (hexosaminidase and acid-phosphatase) measured in the effector cell population parallels cytolysis activation. IFN and IFN inducers (PIC) treatment of cultured murine L-929 cells generate molecular mediated cytolysis. An increase of hydrolytic enzyme activity (hexosaminidase; B-glucuronidase, acid and alkalin phosphatases) precedes cell lysis. Thus, in both cytolytic systems, IFN induced a polyenzymatic activation of hydrolases. This activation is similar to coordinate enzyme induction discovered by Hosli [16] in pathological and experimental instances, when absorbed substrates cannot be hydrolyzed by lack of specific enzymes. Activation of hydrolytic enzymes induced by IFN which determines its enhancing effect on CMC and on fibroblast autolysis [17] could speculatively explain other effects of IFN such as antiviral action, diminution of cell protein synthesis, inhibition of cell division or molecular alterations of cell surface.

Alkaline Phosphatase↗
PubMed1988

Synergistic stimulation of S-adenosylmethionine decarboxylase activity by Ca2+ ionophore A23187, cholera toxin and 1-oleoyl-2-acetylglycerol.

The Ca2+ ionophore A23187 induced S-adenosylmethionine decarboxylase in guinea-pig lymphocytes, and cholera toxin stimulated the induction synergistically. The activator of protein kinase C, 1-oleoyl-2-acetylglycerol, did not induce S-adenosylmethionine decarboxylase activity but potentiated the enzyme activity induced by A23187 or by A23187 and cholera toxin. The addition of both A23187 and cholera toxin induced S-adenosylmethionine decarboxylase, but the further addition of 1-oleoyl-2-acetylglycerol or 12-O-tetradecanoylphorbol 13-acetate did not potentiate the enzyme induction in protein kinase-C-down-regulated cells that had been treated with 12-O-tetradecanoylphorbol 13-acetate for 18 h. These results suggest that a Ca2+-dependent pathway, other than that for protein kinase C, is essential for the induction of S-adenosylmethionine decarboxylase and that a cAMP-dependent pathway and also protein kinase C are involved in the potentiation of the induction.

Adenosylmethionine Decarboxylase↗
PubMed1994

Assessment of cytochrome P4502E1 induction in alcoholic patients by chlorzoxazone pharmacokinetics.

Chlorzoxazone is mainly metabolized to 6-hydroxychloroxazone (6-OHchlorzoxazone) by the ethanol-inducible cytochrome P450 2E1 (CYP2E1). To evaluate the impact of ethanol consumption on the enzyme induction, the pharmacokinetics of chlorozoxazone and 6-OHchlorzoxazone were studied in alcoholic and control subjects. Fifteen alcoholic male inpatients (all smokers, daily intake 333 +/- 191 g of absolute ethanol) and 20 healthy male volunteers (10 smokers and 10 non-smokers, weekly intake < 100 g of absolute ethanol) participated in this study. Following a 12 hr fasting period, each subject was orally administered 500 mg of chlorzoxazone. Venous blood and urine samples were collected over a 10 hr period. Areas under the curve of plasma concentration versus time (AUC) of chlorzoxazone and 6-OHchlorzoxazone was calculated. The total plasma clearance of chlorzoxazone was measured as the dose/AUC ratio. The mean total plasma clearance was not different between smoker and non-smoker controls but it was enhanced by 73% in alcoholic patients. These results indicate a negligible and non-significant effect of cigarette smoking in controls but an increased metabolism of chlorzoxazone in alcoholic patients (P < 0.05). This increase was corroborated by the 2-fold enhancement of the 6-OHchlorzoxazone/chlorzoxazone AUC ratio, compared to controls. A good correlation was found between this AUC ratio and the 6-OHchlorzoxazone/chlorzoxazone concentration ratio at t = 2 hr in patients and in controls (r = 0.88 and 0.85, respectively, P < 0.01). The concentration ratio increased by 150% in alcoholic patients and decreased by 65% in the seven alcoholics tested after 7 days of alcohol abstinence. It is therefore concluded that the 6-OHchlorzoxazone/chlorzoxazone concentration ratio at t = 2 hr could constitute a simple and non-traumatic marker of CYP2E1 induction.

Adult↗
PubMed1981

Lectins mimic insulin in the induction of tyrosine aminotransferase.

Various lectins were found to induce tyrosine aminotransferase in H-35 rat hepatoma cells grown in monolayer culture. Wheat germ agglutinin gave a maximal induction of tyrosine aminotransferase 6 hours after its addition. The induction time course was similar to that elicited by insulin. Fourteen micrograms of wheat germ agglutinin per milliliter gave half-maximal enzyme induction and 50 micrograms per milliliter gave the maximal response. The induction of tyrosine aminotransferase by wheat germ agglutinin was additive with the induction by either dexamethasone or dibutyryl adenosine 3',5'-monophosphate, but was not additive with the tyrosine amino transferase induction by insulin. Wheat germ agglutinin also mimicked insulin in the inhibition of cellular protein degradation in the absence of serum. The insulin-like effects of lectins should be considered in lectin-mediated manipulations such as agglutination.

Animals↗
PubMed1975

Triggering mechanism of B lymphocytes. II. Induction of ornithine decarboxylase in B cells by anti-immunoglobulin and enhancing soluble factor.

In vitro stimulation of rabbit lymphocytes with anti-immunoglobulin antibody (anti-Ig) induced ornithine decarboxylase (ODC) (EC4.1.1.17) in the cells. The enzyme activity reached the maximum at 8 hr after stimulation of the cell with antibody and returned to the unstimulated level after 20 hr. The optimum concentration of antibody to produce the maximum activity of ODC was 25 mug/ml, which was in the same range that required for the maximum production of IgG and the highest rate of DNA synthesis. ODC was again induced with soluble factor (SF) in the cells that had been previously treated with anti-Ig antibody for 24 hr. The treatment of the cells with anti-thymocyte serum and complement did not affect the activity of the enzyme induced by anti-Ig or by SF, indicating that enzyme induction was an event occurring in B cells and not in T cells. The addition of mitotic inhibitors, such as hydroxy-urea (HU) or cytosine arabinoside (Ara-C), to the culture with anti-Ig did not inhibit the production of ODC. The presence of cytochalasin-B with anti-Ig did not inhibit, but rather enhanced, the synthesis of ODC. On the other hand, the presence of HU or cytochalasin-B with soluble factor completely suppressed the induction ODC. These results suggested that intracellular events that trigger the induction of ODC by the interaction of Ig receptor with anti-Ig may be different from the events that induce the same enzyme triggered by SF.

Animals↗
PubMed1983

Induction of hepatic alkaline phosphatase by colchicine: role of cholestasis and bile acids.

We studied the induction of hepatic alkaline phosphatase by colchicine, a drug which impairs bile flow. By analogy to bile duct obstruction, where retained bile acids induce alkaline phosphatase, we hypothesized that the mechanism of induction involves the drug's cholestatic property and subsequent intrahepatic retention of bile acids. After administering colchicine to bile-fistula rats, we monitored bile flow. In colchicine-treated rats which did not develop cholestasis, we varied the transhepatic flux of taurocholate 15-fold over the physiologic range in order to study the role of intrahepatic bile acids. Induction of alkaline phosphatase was observed when cholestasis was absent and the bile acid flux was 5% of normal. The magnitude of enzyme induction was not augmented by increasing the transhepatic flux of taurocholate. The results demonstrate that colchicine induces hepatic alkaline phosphatase by a mechanism which operates independently of cholestasis and is not modified by the level of bile acid in the liver.

Alkaline Phosphatase↗
PubMed1982

Regulation of phosphoenolpyruvate carboxykinase (GTP) synthesis in rat liver cells. Rapid induction of specific mRNA by glucagon or cyclic AMP and permissive effect of dexamethasone.

Isolated rat liver cells maintained in suspension culture for 4 to 5 h synthesize the gluconeogenic cytosolic enzyme phosphoenolpyruvate carboxykinase at a rate approximately 5-fold lower than the in vivo hepatic rate. Glucagon rapidly re-induces phosphoenolpyruvate carboxykinase synthesis in such cells. The rate of enzyme synthesis doubles in 40 min and plateaus at a level 6- to 13-fold higher than in control cells 120 min after glucagon addition at maximal concentration. Consistent with the presumed role of cyclic AMP as a mediator of enzyme induction, the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine, added simultaneously with glucagon, shifts the hormone dose-response curve 2 log units to the left. Moreover, cyclic AMP supplied exogenously to the cells mimics the inductive effect of glucagon. Total cellular RNA isolated from hepatocytes induced by glucagon contains an increased level of mRNA coding for phosphoenolpyruvate carboxykinase, as determined by translational assay. The kinetics and extent of the rise in mRNA level are adequate to explain the stimulation of enzyme synthesis. Although glucagon on its own induces a build-up of phosphoenolpyruvate carboxykinase mRNA and a commensurate stimulation of enzyme synthesis, the glucagon induction is very markedly amplified when the cells are first preincubated with dexamethasone. The glucocorticoid by itself, however, does not have any substantial effect on the level of phosphoenolpyruvate carboxykinase mRNA or on the rate of enzyme synthesis. Its role can therefore be characterized as permissive.

Animals↗
PubMed1981

Induction of pulmonary indoleamine 2,3-dioxygenase by interferon.

Pulmonary indoleamine 2,3-dioxygenase [indoleamine: oxygen 2,3-oxidoreductase(decyclizing)] has been found to be induced (30- to 100-fold) in the mouse after a single intraperitoneal administration of bacterial endotoxin [Yoshida, R. & Hayaishi, O. (1978) Proc. Natl. Acad. Sci. USA 75, 3998-4000] or during in vivo virus infection [Yoshida, R., Urade, Y., Tokuda M. & Hayaishi, O. (1979) Proc. Natl. Acad. Sci. USA 76, 4084-4086]. In the present study, an in vitro system with mouse lung slices was developed in which bacterial endotoxin (5 micrograms/ml)produced an induction (approximately 10-fold) of indoleamine 2,3-dioxygenase. The endotoxin was substituted by interferon from mouse L cells or mouse brain. The pulmonary enzyme activity increased almost linearly for 48 hr after addition of mouse interferon (10(4) units/ml) to lung slices. Interferon from mouse L cells or mouse brain produced a 10- to 15-fold increase in the enzyme activity, whereas that from human leukocytes was all but ineffective. The effect also was observed using highly purified L-cell interferon, prepared by poly(U) affinity column chromatography. When interferon was treated either by heat, alpha-chymotrypsin, or anti-interferon serum, such increase in the enzyme activity was diminished essentially to the same extent as seen in the antiviral activity. The increase in the enzyme activity was blocked when actinomycin D or cycloheximide was added to the slices before interferon treatment. These results suggest that the enzyme induction was produced by interferon and not by possible contaminants in the interferon preparations.

Animals↗
PubMed1993

Dependence of induction of enterobacterial AmpC beta-lactamase on cell-wall peptidoglycan, as demonstrated in Proteus mirabilis and its wall-less protoplast L-form.

The mobilizable plasmid pMD101 (ampR, ampC) was constructed by inserting cloned ampC, the structural gene for the chromosomal AmpC beta-lactamase of Citrobacter freundii, and the closely linked ampR encoding the transcriptional regulator essential for enzyme induction, into the broad host-range plasmid pKT231. Plasmid pMD101 was transconjugated into Proteus mirabilis VI and its isogenic, cell-wall-less protoplast L-form LVI. AmpC beta-lactamase was expressed constitutively from cloned ampR and ampC in bacteria and in some L-form protoplasts. However, induction of the enzyme by beta-lactam antibiotics occurred only in bacterial cells and not in the cell-wall- and peptidoglycan-deficient L-form. In agreement with current models, induction of AmpC beta-lactamase is thought to be initiated by an induction signal arising from the metabolic disturbance of cell-wall peptidoglycan.

Bacterial Proteins↗