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

This study addresses the question whether urinary polyamine excretion is related to cell death or cell proliferation. CCl4 intoxication of the rat was used as the experimental model. Treatment with CCl4, a hepatotoxic haloalkane, produces an initial phase of liver cell death succeeded by a regenerative phase of growth, during which the liver is restored. The highest rate of putrescine (and spermidine) excretion occurred during the first 24 hr of CCl4 intoxication and coincided with the period of maximum liver damage. During subsequent liver regeneration the rate of excretion of both polyamines decreased.
Exp Mol Pathol 1983 Apr
PMID:Urinary polyamine excretion as related to cell death and cell proliferation induced by carbon tetrachloride intoxication. 683 48

The fidelity of liver mtDNA polymerase was compared in control mice, in mice treated chronically with diethylnitrosamine (DEN), carbon tetrachloride (CCl4), or phenobarbital sodium (PBNa). Liver mitochondria were isolated, and the mtDNA polymerase activity was obtained by high-salt extraction and subjected to chromatography first on DEAE-cellulose (DE 52) and then on heparin-Sepharose. Fidelity of the mtDNA polymerase was determined, after heparin-Sepharose chromatography, by measuring the relative incorporation of a complementary nucleotide, [32P]dTMP, and a noncomplementary nucleotide, [3H]dGMP, into acid-precipitable material with enzyme activity directed by the template-primer poly(A) . oligo(dT) 12-18. A decrease in fidelity (increase in relative incorporation [3H]dGMP) was observed after 12 or 13 weeks of treatment with DEN. The fidelity of mouse liver mtDNA polymerase also was decreased after 12 weeks of treatment with PBNa. By contrast, treatment for 12 weeks with CCl4 was accompanied either by increased fidelity (decrease in the relative incorporation of [3H]dGMP) or no change in fidelity.
Mol Pharmacol 1983 Sep
PMID:The fidelity of mouse liver mitochondrial DNA polymerase following long-term administration of carbon tetrachloride, diethylnitrosamine, or phenobarbital. 688 74

The dynamics of glucose movement across perfused livers were assessed in carbon tetrachloride (CCl4)-injured rats. Rats were given CCl4 for 8 weeks and became glucose intolerant and hyperinsulinemic. The fasted rat liver was cyclically perfused with 4 mM lactate and various concentrations (0-20 mM) of glucose for 20 min. In the CCl4-injured liver, net glucose output was less suppressed at high glucose levels than in the normal liver (147 +/- 70 vs 18 +/- 10 mumol at 20 mM glucose, P < 0.05). Deposition of the carbon from [14C] glucose into glycogen was stimulated at high glucose levels and was markedly reduced in the CCl4-injured liver compared to the normal liver (0.58 +/- 0.33 mumol vs 1.44 +/- 0.20 mumol at 20 mM, P < 0.01). Conversion of [14C] lactate to [14C] glucose was not different between the CCl4-injured and the normal liver at each glucose level. Deposition of the carbon from [14C] acetate into glycogen in the CCl4-injured liver was larger than that in the normal liver at 0 mM glucose (0.81 +/- 0.15 mumol vs 0.32 +/- 0.06 mumol, P < 0.01), but was similar to the normal at 20 mM glucose. In the CCl4-injured liver, utilization of exogenous glucose was impaired at high glucose levels, and gluconeogenetic activity was not impaired at low glucose levels. These changes in the hepatic glucose metabolism seem to account for postprandial hyperglycemia without fasting hypoglycemia associated with liver diseases.
Biochem Mol Med 1995 Feb
PMID:Impaired glucose uptake and intact gluconeogenesis in perfused rat liver after carbon tetrachloride injury. 755 15

Orthotopic hepatic transplantation is the most diffused surgical treatment used when attempting to substitute an irreversibly damaged liver. However, this practice faces two main problems. Firstly, surgeons need to explant the organ from the donor who is a just deceased human being, with all the implications involved. Secondly, the host patient must be rendered immunologically tolerant to the graft, through pharmacological suppression. Some hepatic alterations allow a structural and functional compensation by means of an autotransplant, but liver cirrhosis, which is widely diffused in humans and easily produced in experimental animals, has not yet been treated with this technique. This research was undertaken with the aim of procuring hepatic cirrhosis in a medium-sized animal--the rabbit--exposed for some months to CCl4 vapours. Preliminary experiments were performed in order to shorten the challenge period by means of liver induction. This approach was unsuccessful because of the natural susceptibility of this species, which was heightened by the barbiturate administration (0.05% sodium phenobarbital in drinking water, for one week). However, induction, rendered impossible the survival after carbon tetrachloride given orally (125 microliters/kg body weight) or by inhalation (1000 ppm for 2 hours). Finally, CCl4 was administered to normal rabbits by inhalation at the initial concentration of 100 ppm, for 2 hours twice a week. The level of the hepatotoxin was subsequently raised stepwise, according to the body weight curve, up to the maximum of 600 ppm by week 23. At the fourth week of intoxication, the metabolic activity of liver microsomes appeared severely depressed, as shown by the 300% increase of hexobarbital sleeping time. The observation of the surface of liver in situ, performed through an explorative laparatomy, showed initial but clear signs of hepatic fibrosis. At sacrifice, after six or ten months of cirrhogenic treatment, the histopathology examination of the liver demonstrated severe and massive cirrhosis, respectively for the two different steps. This experimental schedule appears to be suitable for producing hepatic cirrhosis in a medium-sized animal, which could be used as a model for pioneering attempts of liver autotransplantation. Furthermore, we point out two important aspects of these results. First, the poison has been inhaled by the experimental animals as it generally happens for humans in the environment. Second, the ratio between the length of exposure versus the life span of rabbits--6 months and 8 years, respectively--parallels that reported for human cirrhosis due to halogenated hydrocarbons--5 or 10 years versus 60 or 80 years.
Res Commun Mol Pathol Pharmacol 1995 Apr
PMID:Experimental model of cirrhosis in rabbits exposed to carbon tetrachloride by inhalation. 762 Aug 39

In previous studies from our laboratory evidence was provided that generation in vivo of dithiothreitol (DTT) from DTT tetraacetate (DTTAC) was accompanied with preventive effects against CCl4-induced necrogenic effects on the liver. In that study, we reported the ability of treatment to decrease the intensity of covalent binding (CB) of the CCl4 reactive metabolites to cellular components but no evidence of preventive effects on CCl4-induced lipid peroxidation (LP) was obtained by the diene hyperconjugation technique. Now, we report that DTT at concentrations 1 or 3 mM inhibit at steps of the process after diene conjugation and prior to malondialdehyde formation. One of those steps might involve peroxides since we observed that DTT is able to significantly react with benzoyl peroxide in a model system. Others might also involve free radicals for in the present study we observed the reaction of DTT with trichloromethyl or trichloromethylperoxy free radicals generated from CBrCl3 in a model system. Reactions of DTT with free radicals and peroxides resulting in inhibition of CB and LP might be critical components in the preventive effects of DTTAC against CCl4-induced liver damage.
Res Commun Mol Pathol Pharmacol 1995 May
PMID:Dithiothreitol inhibitory effects on carbon tetrachloride-promoted NADPH-dependent lipid peroxidation in liver microsomal suspensions. 767 Aug 52

Nicotinamide (NIC) is known to increase the synthesis of pyridine nucleotides and also to inhibit the hydrolysis of them to ADP-ribose, which in turn is involved in Ca2+ release from mitochondria via the ADP ribosylation of crucial mitochondrial proteins. In this work, we test the potential ability of NIC to be a late protective agent against CCl4-induced liver necrosis. We observed that 1 g/kg po NIC, 30 min before or 6 or 10 hr after CCl4 (1 ml/kg), given ip as a 20% (v/v) solution in olive oil, was able to significantly prevent the necrogenic effect of the hepatotoxin at 24 hr as evidenced by determination of isocitric dehydrogenase activity in plasma or by histological observation. NIC administration 6 hr after CCl4 prevented fatty liver induced by hepatotoxin at 24 hr. NIC did not modify CCl4-induced lipid peroxidation process at 1 hr after CCl4 and decreased the covalent binding of 14CCl4 to lipids. NIC decreased the levels of 14CCl4 reaching the liver when given 30 min before hepatotoxin but not when given 6 hr after it. NIC lowered body temperature of rats at 1, 3, and 6 hr and augmented it at 24 hr after CCl4. NIC concentrations in liver as determined by GC/MS/SIM analysis were 21 micrograms/g liver 1 hr after administration and 53 micrograms/g at 3 hr. Late preventive effects of NIC against CCl4 induced liver necrosis when given at 6 or 10 hr after CCl4 are compatible with the hypothesis that NIC restores mitochondrial ability for Ca2+ uptake. This hypothesis remains to be proved and is being further challenged in our laboratory.
Exp Mol Pathol 1994 Jun
PMID:Nicotinamide late protective effects against carbon tetrachloride-induced liver necrosis. 795 79

The change in calcium-binding protein regucalcin, mainly localized in liver, in the liver and serum of rats received a single oral administration of carbon tetrachloride (50%; 1.0 ml/100 g body weight) was investigated. The change of regucalcin mRNA levels in the liver was analyzed by Northern blotting using liver regucalcin cDNA (0.6 kb). At 10 and 24 h after the administration, liver regucalcin mRNA levels were reduced markedly. Moreover, regucalcin concentrations in the liver and serum was estimated by enzyme-linked immunoadsorbent assay (ELISA) with rabbit-anti-regucalcin IgG. Administration of carbon tetrachloride (CCl4) induced a significant decrease in liver regucalcin concentration and a corresponding elevation of serum regucalcin concentration at 24 h after the administration. An appreciable increase in serum regucalcin concentration was seen at 2 h after the administration. Meanwhile, serum transaminases (GOT and GPT) activities were significantly increased by CCl4 administration, indicating that liver injury is induced. The present study demonstrates that hepatic regucalcin is released into the serum of rats administered orally CCl4, suggesting that the estimation of serum regucalcin is a useful tool for diagnosis of liver injury.
Mol Cell Biochem 1994 Feb 23
PMID:Hepatic calcium-binding protein regucalcin in released into the serum of rats administered orally carbon tetrachloride. 803 83

Earlier studies showed that hepatotoxicant-treated experimental animals were more susceptible than controls to the lethal effects of bacterial endotoxin. The exact mechanisms of this effect were not understood. In this paper we showed that nitric oxide (.NO) was produced in whole blood and in liver tissues of rats that had been treated with a nonlethal dose of CCl4 (1.3 g/kg) followed by a low dose of lipopolysaccharide (LPS) (100 micrograms/kg). EPR spectroscopy was used in this study to detect nitrosyl-protein complexes. Hemoglobin-nitrosyl complexes were detected in both whole blood and liver. By performing analyses of EPR spectra obtained from hepatocytes exposed to .NO, we were able to identify EPR signals attributable to nitrosyl-cytochrome P420 in rat liver. We found that nitrosyl complex formation in red blood cells and liver was inhibited by treatment with NG-mono-methyl-L-arginine, suggesting enzymatic biosynthesis of .NO. A small but significant inhibition of nitrosyl complex formation by gadolinium trichloride pretreatment was found in the liver, suggesting that Kupffer cells were also involved in .NO biosynthesis, because this treatment decreased Kupffer cells. There was a synergistic effect of CCl4 and LPS on the serum levels of the hepatic enzymes aspartate aminotransferase, alanine amino-transferase, lactate dehydrogenase, and sorbitol dehydrogenase, which are indices of parenchymal cell damage. NG-Mono-methyl-L-arginine treatment increased these hepatic enzyme activities, suggesting a protective role for .NO. EPR resonances at g approximately 2.48, 2.29, and 1.91, due to low-spin cytochromes P450/P420 (FE3+), were decreased in the livers of LPS-induced rats that had been previously treated with CCl4, indicating cytochrome P450/P420 destruction or at least a change in the valence state of the cytochrome P450/P420 heme groups to Fe2+ in the presence of .NO. Because nitrosyl-cytochrome P450 is not stable, the concomitant detection of nitrosyl-cytochrome P420 (Fe2+) could account, at least in part, for the decrease of the ferric low-spin heme groups. Our novel observations of hepatic nitrosyl species suggest that .NO plays an important role during hepatic injury caused by CCl4 in hosts exposed to endotoxin.
Mol Pharmacol 1994 Aug
PMID:Nitric oxide production during endotoxic shock in carbon tetrachloride-treated rats. 807 2

Interaction of rat hepatocytes with laminin, the major basement membrane adhesive glycoprotein was studied. Rat fetal hepatocytes attached more to laminin than adult hepatocytes. Laminin promoted attachment of fetal hepatocytes in a concentration dependent manner and showed saturable binding pattern. Hepatocytes from CCl4 induced regenerating rat liver also attached more to laminin. The pentapeptide YIGSR derived from laminin promoted attachment of adult and fetal hepatocytes, but to a lesser extent. A 67 kDa protein was isolated from the hepatic plasma membrane of CCl4 induced regenerating rat liver by affinity chromatography over laminin sepharose. This protein appeared to be relatively abundant in regenerating liver than in normal liver. The radioiodinated 67 kDa protein could be inserted into liposomes and these liposomes attached to coverslips coated with laminin in a concentration dependent manner in a divalent cation free medium. Its specificity for laminin was also revealed by absence of significant binding to fibronectin and collagen.
Biochem Mol Biol Int 1993 Oct
PMID:Isolation and characterization of laminin binding protein from regenerating rat liver plasma membrane. 827 10

Treatment of mice with hepatic carcinogens, including CCl4, has been shown to rapidly enhance the transcription of endogenous murine leukemia virus-related proviral sequences in the liver. To understand the mechanism for this transcriptional stimulation, we used nuclear protein preparations from mouse livers to perform DNase I protection analyses and identified nuclear protein binding on approximately 20 individual sequences within the regulatory regions of the long terminal repeat (LTR) of a polytropic-class endogenous provirus clone. From 3 to 144 h after treatment with CCl4, the livers of FVB/N mice were analyzed for specific nuclear protein binding to the LTR DNA. Three to nine hours after CCl4 treatment, decreased protection was seen at potential regulatory cis-elements throughout the LTR, including specific sites within the putative negative regulatory element (located 5' of the consensus enhancer sequences) and the 3' terminal portion of the polytropic class-specific enhancer-like inserted sequence element and around the CCAA(C/T) box in the promoter region. In addition, by 3-6 h after treatment, a transient increase in protection activity for the transcription initiation site occurred. The loss of cis-element protection expanded to other binding sites and became most marked by 48 h after treatment. As the regenerating liver recovered, the nuclear protein binding activities for these LTR sequences also recovered, but protection at the TATAA and transcription initiation sites remained deprotected at 144 h after treatment. Nuclear protein protection of other sites, particularly in the conserved LTR enhancer sequences, was minimally affected by CCl4 treatment. Three nuclear protein binding sites that showed rapid CCl4-induced kinetic changes were homologous to the consensus sequence for the binding of the transcription factor families MEF-2, HNF-1, and C/EBP. The complex kinetic changes in factors that may contribute to the rapid and transient induction of endogenous retroviral gene expression in the liver after CCl4 exposure are discussed.
Mol Carcinog 1993
PMID:Carbon tetrachloride induction of rapid changes in liver nuclear protein factors capable of sequence-specific binding to regulatory elements in the long terminal repeat of polytropic-class endogenous murine leukemia virus-related proviruses. 828 Mar 73


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>