scholarly journals Localization and differential induction of cytochrome P450IVA and acyl-CoA oxidase in rat liver

1991 ◽  
Vol 275 (1) ◽  
pp. 247-252 ◽  
Author(s):  
D R Bell ◽  
R G Bars ◽  
G G Gibson ◽  
C R Elcombe
Keyword(s):  
Peroxisome Proliferator ◽  
Peroxisome Proliferators ◽  
Dependent Manner ◽  
Early Markers ◽  
Acyl Coa Oxidase ◽  
Significant Change ◽  
Kinetics Of ◽  
Dose Dependent ◽  
Induced Proteins ◽  
Hepatic Cytochrome

The peroxisome proliferators are structurally diverse chemicals which induce hyperplasia, hypertrophy and the proliferation of peroxisomes in the rodent liver. Cytochrome P450IVA1 and peroxisomal enzymes, such as acyl-CoA oxidase, are induced and are early markers of treatment with peroxisome proliferators. In this study, rats were dosed intraperitoneally with the potent peroxisome proliferator methylclofenapate and the hepatic induction response was studied. There was no significant change in the enzyme activities of laurate hydroxylase (cytochrome P450IVA1) or acyl-CoA oxidase in the first 8 h after treatment, but the activities had doubled at 24 h, suggesting that these enzymes are not involved in the mediation of early events in peroxisome proliferation. Hepatic cytochrome P450IVA1 mRNA was significantly increased at 6 and 8 h after treatment, rising to 15-fold above control values at 30 h. In contrast, acyl-CoA oxidase mRNA showed no significant change in the first 8 h, but increased to 13-fold above control values at 24 and 30 h, thereby demonstrating different kinetics of induction of the two mRNAs. In order to determine whether cytochrome P450IVA1 and peroxisomal enzymes were included in the same cells, rats were treated daily with sub-maximal (2 or 5 mg/kg) and maximal (25 mg/kg) inducing doses of methylclofenapate for 4 days. The lobular distribution of induced proteins was determined immunocytochemically with antibodies raised against P450IVA1 and acyl-CoA oxidase. Livers from control animals showed minimal staining for both proteins. However, in the livers of animals treated with 2 or 5 mg of methylclofenapate/kg, both acyl-CoA and P450IVA immunostaining was increased, mainly in the centrilobular area. Immunostaining of serial sections revealed that these proteins were induced in the same region of the lobule. A maximal inducing dose of methylclofenapate (25 mg/kg) caused panlobular induction of both proteins. The results demonstrate that these proteins are induced in a dose-dependent manner in the same, spatially distinct, sensitive region of the liver lobule.

scholarly journals Kinetics of Mushroom Tyrosinase and Melanogenesis Inhibition byN-Acetyl-pentapeptides

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Ching-Yi Lien ◽  
Ching-Yu Chen ◽  
Shih-Ting Lai ◽  
Chin-Feng Chan
Keyword(s):  
Kojic Acid ◽  
Lag Time ◽  
Melanoma Cells ◽  
Dependent Manner ◽  
Mushroom Tyrosinase ◽  
Inhibitory Effects ◽  
B16f10 Melanoma ◽  
B16f10 Melanoma Cells ◽  
Kinetics Of ◽  
Dose Dependent

We investigated the kinetics of 4N-acetyl-pentapeptides, Ac-P1, Ac-P2, Ac-P3, and Ac-P4, regarding inhibition of mushroom tyrosinase activity. The peptides sequences of Ac-P1, Ac-P2, Ac-P3, and Ac-P4 were Ac-RSRFK, Ac-KSRFR, Ac-KSSFR, and Ac-RSRFS, respectively. The 4N-acetyl-pentapeptides were able to reduce the oxidation ofL-DOPA by tyrosinase in a dose-dependent manner. Of the 4N-acetyl-pentapeptides, only Ac-P4 exhibited lag time (80 s) at a concentration of 0.5 mg/mL. The tyrosinase inhibitory effects of Ac-P4 (IC500.29 mg/mL) were more effective than those of Ac-P1, Ac-P2, and Ac-P3, in which IC50s were 0.75 mg/mL, 0.78 mg/mL, and 0.81 mg/mL, respectively. Kinetic analysis demonstrated that all 4N-acetyl-pentapeptides were mixed-type tyrosinase inhibitors. Furthermore, 0.1 mg/mL of Ac-P4 exhibited significant melanogenesis inhibition on B16F10 melanoma cells and was more effective than kojic acid. The melanogenesis inhibition of Ac-P4 was dose-dependent and did not induce any cytotoxicity on B16F10 melanoma cells.

scholarly journals Effects of penicillins and 6-aminohexanoic acid on the kinetics of human plasmin

1989 ◽  
Vol 260 (2) ◽  
pp. 609-612 ◽  
Author(s):  
A A A Higazi ◽  
M Mayer
Keyword(s):  
Active Site ◽  
Dependent Manner ◽  
Chromogenic Substrate ◽  
Regulatory Site ◽  
Amidolytic Activity ◽  
Plasmin Activity ◽  
Maximal Inhibition ◽  
Sigmoidal Curve ◽  
Kinetics Of ◽  
Dose Dependent

Human plasmin activity is inhibited by various penicillins in a dose-dependent manner. Ampicillin and cloxacillin produce a 50% inhibition of the globinolytic activity of plasmin at 4.5 and 5.3 mM respectively. A lower inhibitory capacity is displayed by carbenicillin. Assay of plasmin by its amidolytic activity on D-valyl-L-leucyl-L-lysine p-nitroanilide dihydrochloride showed that ampicillin at a concentration producing half-maximal inhibition converted the hyperbolic activity-substrate concentration curve into a sigmoidal curve. A similar conversion occurred in the presence of ampicillin when plasmin was assayed with an alternative chromogenic substrate, L-pyroglutamyl-glycyl-L-arginine p-nitroanilide hydrochloride 6-Aminohexanoic acid at 7.5 microM abolished the inhibition of plasmin induced by ampicillin. The present observations suggest that ampicillin interacts with plasmin at a regulatory site different from the active site of the enzyme. The effect of 6-aminohexanoic acid indicates that the lysine-binding site may be part of a regulatory site. It is possible that modulation of plasmin activity by ligands plays a role in the control of fibrinolysis.

scholarly journals Pedigree analyses of yeast cells recovering from DNA damage allow assignment of lethal events to individual post-treatment generations.

Genetics ◽  
1990 ◽  
Vol 124 (1) ◽  
pp. 57-65
Author(s):  
F Klein ◽  
A Karwan ◽  
U Wintersberger
Keyword(s):  
Dna Damage ◽  
Post Treatment ◽  
Yeast Cells ◽  
Dependent Manner ◽  
The Third ◽  
Lethal Mutations ◽  
Dna Damaging Agents ◽  
Kinetics Of ◽  
Dose Dependent ◽  
Insight Into

Abstract Haploid cells of Saccharomyces cerevisiae were treated with different DNA damaging agents at various doses. A study of the progeny of individual such cells (by pedigree analyses up to the third generation) allowed the assignment of lethal events to distinct post treatment generations. By microscopically inspecting those cells which were not able to form visible colonies we could discriminate between cells dying from immediately effective lethal hits and those generating microcolonies (three to several hundred cells) probably as a consequence of lethal mutation(s). The experimentally obtained numbers of lethal events (which we call apparent lethal fixations) were mathematically transformed into mean probabilities of lethal fixations as taking place in cells of certain post treatment generations. Such analyses give detailed insight into the kinetics of lethality as a consequence of different kinds of DNA damage. For example, X-irradiated cells lost viability mainly by lethal hits (which we call 00-fixations); only at a higher dose also lethal mutations fixed in the cells that were in direct contact with the mutagen (which we call 0-fixations), but not in later generations, occurred. Ethyl methanesulfonate (EMS)-treated cells were hit by 00-fixations in a dose dependent manner; 0-fixations were not detected for any dose of EMS applied; the probability for fixation of lethal mutations was found equally high for cells of the first and second post treatment generation and, unexpectedly, was well above control in the third post-treatment generation. The distribution of all sorts of lethal fixations taken together, which occurred in the EMS-damaged cell families, was not random.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Modulation of electrical activity and ionic currents of isolated neurons by orexin A

2013 ◽  
Vol 11 (4) ◽  
pp. 54-60
Author(s):  
Petr Dmitriyevich Shabanov ◽  
Anatoliy Ivanovich Vislobokov
Keyword(s):  
Membrane Potential ◽  
Lymnaea Stagnalis ◽  
Ionic Currents ◽  
Maximal Effect ◽  
Dependent Manner ◽  
Isolated Neurons ◽  
Orexin A ◽  
High Concentrations ◽  
Kinetics Of ◽  
Dose Dependent

The changes in intracellular potential of resting (PR) and potential of action (PA) of the identified neurons of pedal and visceral ganglia of the CNS mollusk Planorbarius corneus registered by means of intracellular electrodes, and ionic currents of isolated neurons under fixed potential after administration of orexin A in concentrations 1, 10, 100 and 1000 µg/ml were studied by the method of fixation of membrane potential in isolated neurons of the Lymnaea stagnalis mollusk. Dibazol in concentrations of 1 and 10 µM effected slightly on the ionic currents. High concentrations of dibazol (100 and 1000 µM) inhibited all currents in dose dependent manner with maximal effect on potassium currents amplitude. ЕС50 were 7.4 мМ for INa, 4.0 мМ for ICa, 83.9 µM for IKs,1 (one group of neurons) and 2.9 мМ for IKs,2 (the another group of neurons). The voltage-amper membrane characteristics shift was not registered, but the kinetics of currents development was changed. Dibazol was more effective in inhibition of ionic currents compared to its structural analogs.

scholarly journals Cevoglitazar, a Novel Peroxisome Proliferator-Activated Receptor-α/γ Dual Agonist, Potently Reduces Food Intake and Body Weight in Obese Mice and Cynomolgus Monkeys

2010 ◽  
Vol 31 (3) ◽  
pp. 404-405
Author(s):  
Hong Chen ◽  
Beatriz Dardik ◽  
Ling Qiu ◽  
Xianglin Ren ◽  
Shari L. Caplan ◽  
...  
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Plasma Levels ◽  
Energy Homeostasis ◽  
Peroxisome Proliferator ◽  
Dependent Manner ◽  
Peroxisome Proliferator Activated Receptor ◽  
Cynomolgus Monkeys ◽  
Dose Dependent ◽  
Dual Agonist

ABSTRACT Cevoglitazar is a dual agonist for the peroxisome proliferator-activated receptor (PPAR)-α and -γ subtypes. Dual activation of PPARα and -γ is a therapeutic approach in development for the treatment of type 2 diabetes mellitus and diabetic dyslipidemia. In this report, we show that, in addition to improving insulin sensitivity and lipid metabolism like other dual PPAR agonists, cevoglitazar also elicits beneficial effects on energy homeostasis in two animal models of obesity. In leptin-deficient ob/ob mice, administration of cevoglitazar at 0.5, 1, or 2 mg/kg for 18 d led to acute and sustained, dose-dependent reduction of food intake and body weight. Furthermore, plasma levels of glucose and insulin were normalized after 7 d of cevoglitazar treatment at 0.5 mg/kg. Plasma levels of free fatty acids and triglycerides were dose-dependently reduced. In obese and insulin-resistant cynomolgus monkeys, treatment with cevoglitazar at 50 and 500 μg/kg for 4 wk lowered food intake and body weight in a dose-dependent manner. In these animals, cevoglitazar also reduced fasting plasma insulin and, at the highest dose, reduced hemoglobin A1c levels by 0.4%. These preclinical results demonstrate that cevoglitazar holds promise for the treatment of diabetes and obesity-related disorders because of its unique beneficial effect on energy balance in addition to improving glycemic and metabolic control.

scholarly journals Peroxisomal Enzymes and 8-Hydroxydeoxyguanosine in Rat Liver Treated with Perfluorooctanoic Acid

2003 ◽  
Vol 19 (1) ◽  
pp. 19-25 ◽  
Author(s):  
Awad Abdellatif ◽  
Ahmad H. Al-tonsy ◽  
Mahmoud E. Awad ◽  
M. Roberfroid ◽  
M. Nezam Ullah Khan
Keyword(s):  
Hepatocellular Carcinoma ◽  
Dna Damage ◽  
Carbon Tetrachloride ◽  
Liver Cancer ◽  
Selection Procedure ◽  
Basal Diet ◽  
Perfluorooctanoic Acid ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferators ◽  
Acyl Coa Oxidase

Although peroxisome proliferators are considered non-genotoxic agents, most of them, nevertheless, were found to promote and/or induce, hepatocellular carcinoma (HCC) in rodents. The aim of the present study is, first, to investigate whether the peroxisome proliferator perfluorooctanoic acid (PFOA) possesses inherent liver cancer promoting activity, and second, to study the possible mechanisms involved. To acheive these aims two protocols have been applied, a biphasic protocol (initiation by diethyl-nitrozamine (DEN) 200 mg/kg i.p. followed by treatment with 0.005% or 0.02% perflourooctanoic acid (PFOA) for 14 and 25 weeks) and a triphasic initiation, selection-promotion (IS) protocol (initiation by giving 200 mg/kg DEN i.p. followed by a selection procedure for 2 weeks consisting of giving 0.03% 2-acetylaminofluorene (2-AAF) in diet). In the middle of this treatment a single oral dose of carbon tetrachloride (2.0 ml/kg) was given, followed by giving diet containg 0.015% of PFOA for 25 weeks. After applying both protocols, our results showed slight increase in the catalase activity while acyl CoA oxidase activity was markedly increased. Both experiments indicated that PFOA has a liver cancer promoting activity. Other groups of rats were given either basal diet or diet containing 0.02% PFOA. Five or nine weeks later they were sacrificed and the levels of 8-hydroxydeoxyguanosine in the isolated DNA were estimated. The data showed a slight nonetheless insignificant increase in 8-hydroxydeoxyguanosine. From the present data, it is concluded that PFOA is a true liver cancer promoter that may not require extensive initial DNA damage for its promoting activity.

scholarly journals Protective Effects of Peroxisome Proliferator-Activated Receptor-αAgonist, Wy14643, on Hypoxia/Reoxygenation Injury in Primary Rat Hepatocytes

PPAR Research ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Ke Chen ◽  
Yuan-Hai Li ◽  
Si-Qi Xu ◽  
Sheng-Hong Hu ◽  
Lei Zhang
Keyword(s):  
Rat Hepatocytes ◽  
Peroxisome Proliferator ◽  
Dependent Manner ◽  
Protective Effects ◽  
Primary Hepatocytes ◽  
Peroxisome Proliferator Activated Receptor ◽  
Group A ◽  
Reoxygenation Injury ◽  
Dose Dependent ◽  
Significant Protective Effect

This study investigates the effects and possible mechanism of an agonist of PPARα, Wy14643, on primary hepatocytes subjected to H/R injury in rats. H/R induced a significant increase ALT, AST, MDA in the culture medium and ROS in the hepatocytes. These effects were reversed by pretreatment with Wy14643 in the dose-dependent manner. The activity of SOD and the level of GSH in the hepatocytes were decreased after H/R, which were increased by Wy14643 pretreatment. Moreover, the mRNA expressions of PPARαsignificantly increased in H/R+Wy14643 groups when compared with that in H/R group. A PPARαagonist, Wy14643, exerts significant protective effect against H/R injury in primary hepatocytes via PPARαactivation and attenuating oxidative stress.

Differential effects of flavonoids on 3T3-L1 adipogenesis and lipolysis

2001 ◽  
Vol 280 (4) ◽  
pp. C807-C813 ◽  
Author(s):  
Anne W. Harmon ◽  
Joyce B. Harp
Keyword(s):  
Structural Similarity ◽  
Peroxisome Proliferator ◽  
Dependent Manner ◽  
Peroxisome Proliferator Activated Receptor ◽  
Differential Effects ◽  
Triglyceride Accumulation ◽  
Induction Of Differentiation ◽  
Mitotic Clonal Expansion ◽  
Dose Dependent ◽  
Inhibit Cell Proliferation

Flavonoids, polyphenolic compounds that exist widely in plants, inhibit cell proliferation and increase cell differentiation in many cancerous and noncancerous cell lines. Because terminal differentiation of preadipocytes to adipocytes depends on proliferation of both pre- and postconfluent preadipocytes, we predicted that flavonoids would inhibit adipogenesis in the 3T3-L1 preadipocyte cell line. The flavonoids genistein and naringenin inhibited proliferation of preconfluent preadipocytes in a time- and dose-dependent manner. When added to 2-day postconfluent preadipocytes at the induction of differentiation, genistein inhibited mitotic clonal expansion, triglyceride accumulation, and peroxisome proliferator-activated receptor-γ expression, but naringenin had no effect. The antiadipogenic effect of genistein was not due to inhibition of insulin receptor subtrate-1 tyrosine phosphorylation. When added 3 days after induction of differentiation, neither flavonoid inhibited differentiation. In fully differentiated adipocytes, genistein increased basal and epinephrine-induced lipolysis, but naringenin had no significant effects. These data demonstrate that genistein and naringenin, despite structural similarity, have differential effects on adipogenesis and adipocyte lipid metabolism.

scholarly journals THE MOLLUSC IONIC CURRENTS CHANGES AFTER ADMINISTRATION OF N-PHENYLALKYL DERIVATIVES OF TAURINE

2012 ◽  
Vol 10 (4) ◽  
pp. 67-72
Author(s):  
Anatoliy Ivanovich Vislobokov ◽  
Lyudmila Konstantinovna Khnychenko ◽  
Yuriy Dmitriyevich Ignatov ◽  
Nikolay Sergeyevich Sapronov ◽  
Petr Dmitriyevich Shabanov
Keyword(s):  
Lymnaea Stagnalis ◽  
Ionic Currents ◽  
Ionic Channels ◽  
Dependent Manner ◽  
Isolated Neurons ◽  
Sodium Potassium ◽  
Fixed Membrane ◽  
Kinetics Of ◽  
Dose Dependent ◽  
Derivatives Of

The transmembrane sodium, potassium and calcium ionic currents were studied after extracellular administration of N-phenylalkyl derivatives of taurine in concentrations 1, 10, 100 and 1000 mM. The method of intracellular dialysis with fixed membrane potential was used in model of isolated neurons of the mollusks Lymnaea stagnalis and Planorbarius corneus. The solutions containing 1 and 10 mM of the compounds studied did not change ionic channels activity in isolated neurons. Concentrations 100 and mM depressed reversibly all currents in the dose-dependent manner: taurine < TAU-02 < TAY-15 < TAU-60. The voltage-amplitude membrane characteristics as well as kinetics of the currents did not change.

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