Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.7.49 (reverse transcriptase)
31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of this work was to study the induction and secretion of interleukin 8 (IL-8) and some oxidative stress parameters after ethanol (EtOH), acetaldehyde (Ac) or lipopolysaccharide (LPS) treatment on HepG2 cells. Cells were treated with 50 mM EtOH, 175 &mgr;M Ac or 1 &mgr;g/ml of LPS. IL-8 induction and secretion were determined in the presence of the toxics, and the effect of antioxidants N-acetyl-L-cysteine and 1,1,3,3-tetramethyl-2-thiourea was evaluated. Further, the effect of adding polyclonal anti-human tumor necrosis factor alpha (TNF-alpha) and H(2)O(2) was studied, and catalase, superoxide dismutase and glutathione peroxidase activities were determined. Lipid peroxidation increased significantly only in Ac-treated cells. All toxics failed to decrease significantly the intracellular levels of reduced GSH. Catalase activity was diminished in all treatments, while other enzyme activities did not present changes. No change in peroxide production was found with any treatment. IL-8 secretion increased in Ac (41%) and in LPS (38%)-treated cells. Antioxidant and anti-TNF-alpha treatments decreased IL-8 secretion. H(2)O(2) (0.25 mM)-treated cells increased IL-8 secretion. IL-8 reverse transcriptase-polymerase chain reaction results correlated with secretion values. Our results show that Ac and LPS treatment produced an increased IL-8 induction and secretion. Oxidative stress and TNF-alpha are mediators in IL-8 response. This observation suggests that in the in vivo liver, the mechanism of ethanol-induced IL-8 production requires ethanol metabolism, and hepatocytes do not require the interaction among different populations of liver cells to respond.
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PMID:Interleukin 8 response and oxidative stress in HepG2 cells treated with ethanol, acetaldehyde or lipopolysaccharide. 1280 41

Here, we show that inhibition of c-Myc causes a proliferative arrest of M14 melanoma cells through cellular crisis, evident by the increase in size, multiple nuclei, vacuolated cytoplasm, induction of senescence-associated beta-galactosidase activity and massive apoptosis. The c-Myc-induced crisis is associated with decreased human telomerase reverse transcriptase expression, telomerase activity, progressive telomere shortening, glutathione (GSH), depletion and, increased production of reactive oxygen species. Treatment of control cells with L-buthionine sulfoximine decreases GSH to levels of c-Myc low expressing cells, but it does not modify the growth kinetic of the cells. Surprisingly, when GSH is increased in the c-Myc low expressing cells by treatment with N-acetyl-L-cysteine, cells escape crisis. To test the hypothesis that both oxidative stress and telomerase dysfunction are involved in the c-Myc-dependent crisis, we directly inhibited telomerase function and glutathione levels. Inactivation of telomerase, by expression of a catalytically inactive, dominant negative form of reverse transcriptase, reduces cellular lifespan by inducing telomere shortening. Treatment of cells with L-buthionine sulfoximine decreases GSH content and accelerates cell crisis. Analysis of telomere status demonstrated that oxidative stress affects c-Myc-induced crisis by increasing telomere dysfunction. Our results demonstrate that inhibition of c-Myc oncoprotein induces cellular crisis through cooperation between telomerase dysfunction and oxidative stress.
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PMID:Inhibition of c-Myc oncoprotein limits the growth of human melanoma cells by inducing cellular crisis. 1282 59

Glutathione (GSH) synthesis is differentially regulated in the embryo and visceral yolk sac (VYS) of the developing rat conceptus. The innate capacity to respond to environmental insult and chemical exposure by inducing de novo GSH synthesis may help to determine overall cell sensitivity and/or resistance to chemically induced malformation. Specific activities of glutamate-cysteine ligase (GCL), the rate limiting enzyme in GSH synthesis, were determined by measuring the formation of gamma-glutamylcysteine (GC) in homogenates prepared from rat embryos and VYSs. GC formation increased linearly with time and with relative protein concentration. Specific activities were found to be 60.5 +/- 3.2 and 118.9 +/- 4.2 pmol GC/mg protein/min in the gestational day (GD) 10 embryo and VYS, respectively, and 22.7 +/- 0.4 and 71.3 +/- 0.6 pmoles GC/mg protein/min in the respective GD 11 embryo and VYS. Apparent kinetic constants determined from embryo and VYS homogenates gave respective apparent K(m) values for glutamate of 0.75 and 1.38 mM and for cysteine 0.03 mM in both tissues. Apparent V(max) values were higher in the VYS in each case, corresponding with a lower apparent K(m) and higher GCL activity. GCL specific activities increased significantly following a 24 h in vitro exposure to diethyl maleate (DEM) and diamide, but remained unchanged following exposure to prostaglandin A(2) (PGA(2)) and t-butylated hydroxytoluene (BHT). Basal expression of GCL catalytic subunit (GCL(C)) and regulatory subunit (GCL(R)) was 59- and 25-fold higher in VYS, respectively, compared to the embryo. Quantitative real-time fluorescence reverse transcriptase polymerase chain reaction (RT-PCR) showed that following DEM and diamide treatment, GCL(C) expression increased up to 19-fold in embryonic tissues but was not induced in the VYS. Only DEM increased the expression of the light/regulatory subunit GCL(R) in the embryo (8-fold). Densitometry of immunoblots revealed approximately 75% more GCL(C) in the VYS than in the embryo. Following treatments, a marked increase was induced in embryonic GCL(C) content with both DEM (85%) and diamide (19%), but in the VYS, only DEM caused an increase in GCL(C) protein (38%).
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PMID:Spatial activities and induction of glutamate-cysteine ligase (GCL) in the postimplantation rat embryo and visceral yolk sac. 1511 89

Glutathione S-transferases (GSTs) are scavenging enzymes that detoxify cellular xenobiotics and toxins by catalyzing the conjugation of these substrates with a tripeptide glutathione. GSTs are classified depending on gene organization and sequence similarity. The sequence analysis of genomic DNA for zeta class GST (GSTZ) locus in rice indicated that two homologous GSTZ genes lay in a tandem orientation with a short (0.4 kb) intergenic spacer. The upstream OsGSTZ1 and downstream OsGSTZ2 spanned 3.5 and 3.2 kb with nine coding exons, respectively. The transcript of OsGSTZ1 had a long 3' untranslated region (3' UTR) that was mostly encoded by a 10th noncoding exon, whereas OsGSTZ2 mRNA contained a long 5' UTR. Northern blot analysis showed that OsGSTZ1/2 messages were strongly expressed in leaf blades, while transcripts from roots were low level. Because OsGSTZ1/2 messages in leaf tissues were strongly induced only by water treatment, it was difficult to assay for the induction of OsGSTZ1/2 transcripts by various stress treatments. Thus, using rice culture cells, we analyzed the respective responses of OsGSTZ1 and OsGSTZ2 genes against various treatments by real-time reverse transcriptase-polymerase chain reaction (RT-PCR). The results showed that OsGSTZ1 was expressed at a level ca. 1000-fold higher than OsGSTZ2 in suspension cells without stress treatment. OsGSTZ1 was expressed constitutively under various stress conditions. In contrast, the expression of OsGSTZ2 gene was strongly enhanced to 30-fold by treatment with jasmonic acid. These observations suggested that the expression of OsGSTZ1 and OsGSTZ2 genes are differentially regulated in the culture cell of rice.
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PMID:Genomic structure and differential expression of two tandem-arranged GSTZ genes in rice. 1519 97

In the present study, we investigated the protective effect of Lycium chinense Miller (Solanaceae) fruit (LFE) against CCl(4)-induced hepatotoxicity and the mechanism underlying these protective effects in rats. The pretreatment of LFE has shown to possess a significant protective effect by lowering the serum aspartate and alanine aminotransferase (AST and ALT) and alkaline phosphatase (ALP). This hepatoprotective action was confirmed by histological observation. In addition, pretreatment of LFE prevented the elevation of hepatic malondialdehyde (MDA) formation and the depletion of reduced glutathione (GSH) content and catalase activity in the liver of CCl(4)-injected rats. The LFE also displayed hydroxide radical scavenging activity in a dose-dependent manner (IC(50) = 83.6 microg/ml), as assayed by electron spin resonance (ESR) spin-trapping technique. The expression level of cytochrome P450 2E1 (CYP2E1) mRNA and protein, as measured by reverse transcriptase-polymerase chain reaction (RT-PCR) and western blot analysis, was significantly decreased in the liver of LFE-pretreated rats when compared with that in the liver of control group. Based on these results, it was suggested that the hepatoprotective effects of the LFE might be related to antioxidative activity and expressional regulation of CYP2E1.
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PMID:Protective effect of Lycium chinense fruit on carbon tetrachloride-induced hepatotoxicity. 1561 74

Tibial dyschondroplasia (TD) is a metabolic cartilage disease of young poultry in which endochondral bone formation is disrupted leading to the retention of a non-calcified, avascular plug of cartilage in the tibial growth plate. Chicks aged 7 days were fed either a control diet or one containing thiram 100 ppm for 48 h to induce TD. Cell multiplication in the growth plate was determined thereafter with bromodeoxyuridine (BrdU) labelling, and metabolic changes by measuring alkaline phosphatase (ALP), tartrate-resistant acid phosphatase (TRAP), and glutathione (GSH) activities. The effect on chondrocyte maturation was examined by reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of gene expression. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) and DNA fragmentation were used to determine the effects of thiram on cell survival. The results showed that thiram-induced TD was not due to the multiplication of cells in the post-proliferative zones. Thiram did not affect ALP activity, which would have indicated a loss of calcification potential, but it reduced both TRAP and the glutathione concentrations, suggesting that the growth plate metabolism and remodelling functions were adversely affected. Thiram appeared to have no effect on the expression of type X collagen, transglutaminase, RUNX2, or matrix metalloproteinase-2 (MMP) genes suggesting that it did not alter the maturation potential of chondrocytes. On the contrary, the expressions of MMP-13 and vascular endothelial growth factor (VEGF) genes were "up-regulated," suggesting that thiram has pro-angiogenic activity. However, TUNEL assay showed that thiram induced endothelial cell apoptosis in the capillary vessels of the growth plates, as early as 10 days of age, when TD was not visually evident. The vascular death increased on subsequent days accompanied by massive death of chondrocytes in the transition zone of the growth plate. The induction of apoptosis in the growth plate was also demonstrated by DNA fragmentation. It was concluded that thiram induced TD not through an increase in the multiplication of chondrocytes in the transition zone and not by altering the expression of genes causing the arrest of chondrocytes in a prehypertrophic state, but by creating a metabolic dysfunction which led to the destruction of blood capillaries in the transition zone chondrocytes.
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PMID:Changes in the tibial growth plates of chickens with thiram-induced dyschondroplasia. 1589 90

Inherited defects of copper metabolism resulting in hepatic copper accumulation and oxidative-stress might cause breed-associated forms of hepatitis. Biliary excretion is the major elimination route of copper, therefore increased hepatic copper concentrations could also be caused by cholestasis. The aim of this study was to find criteria to determine whether copper-accumulation is primary or occurs secondary to hepatitis. Liver samples of Bedlington Terriers with copper toxicosis (CT), breeds with non-copper-associated chronic extrahepatic cholestasis (EC) or chronic hepatitis (CH), and healthy dogs were used. Copper metabolism was analyzed by means of histochemical staining (copper concentration) and quantitative reverse transcriptase polymerase chain reaction (Q-PCR) on copper excretion/storage (ATOX1, COX17, ATP7A, ATP7B, CP, MT1A, MURR1, XIAP). Oxidative stress was measured by determining GSH/GSSG ratios and gene-expression (SOD1, CAT, GSHS, GPX1, CCS, p27KIP, Bcl-2). Results revealed 5+ copper in CT, but no or 1-2+ copper in EC and CH. Most gene products for copper metabolism remained at concentrations similar to healthy dogs. Three clear exceptions were observed in CT: 3-fold mRNA increase of ATP7A and XIAP and complete absence of MURRI. The only quantitative differences between the diseased and the control groups were in oxidative stress, evidenced by reductions in all GSH/GSSG ratios. We conclude that 3+ or higher histochemical detection of copper indicates a primary copper storage disease. The expression profile of copper-associated genes can be used as a reference for future studies on copper-associated diseases. All 3 diseases have reduced protection against oxidative stress, opening a rationale to use antioxidants as possible therapy.
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PMID:Copper metabolism and oxidative stress in chronic inflammatory and cholestatic liver diseases in dogs. 1706

Ginkgo biloba extract has been shown to be hepatoprotective. However, its benefits when used in alcoholic liver injury have not been demonstrated. This study investigated the effects of Ginkgo biloba extract on alcohol-induced liver injury in a chronic alcohol plus fish oil gavage model in rats. Liver injury was evaluated histologically and by serum alanine aminotransferase (ALT). Liver tumor necrosis factor-alpha (TNF-alpha) protein levels, malondialdehyde (MDA) and glutathione (GSH) contents were determined. TNF-alpha mRNA expression in the liver was analysed by reverse transcriptase-polymerase chain reaction (RT-PCR). Rats given fish oil plus alcohol developed macrovesicular and microvesicular steatosis, spotty necrosis and mild inflammation in the liver and elevated serum ALT levels, which were accompanied by increased MDA contents, reduced GSH contents and elevated TNF-alpha protein and mRNA expressions in the liver. Supplementation with Ginkgo biloba extract (200 mg/kg, orally) improved the liver injury, blunted the rises of MDA contents and TNF-alpha expression, and restored the GSH content in the liver. Ginkgo biloba extract protects against alcohol-induced liver injury, and the mechanism may involve a reduction of lipid peroxidation, prevention of GSH depletion and inhibition of TNF-alpha expression in the liver.
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PMID:Ginkgo biloba extract protects against alcohol-induced liver injury in rats. 1715 34

Retinoids play important roles in many diverse biological functions such as cell growth, morphogenesis, differentiation, and reproduction. Previous studies demonstrated that retinol administration to ewes, followed by natural service, resulted in embryos with improved competence to develop under standard in vitro conditions (5% CO(2) in air). Additional studies provided evidence that retinol may have some antioxidant effect by improving blastocyst development in cattle under atmospheric conditions (5% CO(2) in air). Glutathione is an important non-protein, sulphydryl compound found in oocytes and embryos, which acts to decrease oxidative stress. The purpose of the present study was to evaluate the effects of retinol administration to ewes on the content of glutathione and glutathione-related and antioxidant enzymes in in vivo matured sheep oocytes. Briefly, ewes were administered retinol or vehicle during superovulation, and after 60h the oviducts were removed and mature oocytes collected. Glutathione content did not differ significantly between oocytes collected from retinol-treated ewes (6.78+/-3.81pmol/oocyte) and control ewes (6.38+/-1.58pmol/oocyte). Transcripts encoding for manganese superoxide dismutase (Mn-SOD), copper zinc superoxide dismutase (Cu-Zn SOD), glutathione synthetase (GS), and glutathione transferase pi (GSTp) were detected in single ovine oocytes; however, semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) analysis did not reveal any significant differences in transcripts between oocytes from retinol-treated ewes and those from control ewes.
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PMID:Glutathione content and antioxidant enzyme expression of in vivo matured sheep oocytes. 1927 97

Nevirapine, a non-nucleoside HIV-1 reverse transcriptase inhibitor, has been associated with incidences of skin rash and hepatotoxicity in patients. Although the mechanism of idiosyncratic hepatotoxicity remains unknown, it is proposed that metabolic activation of nevirapine and subsequent covalently binding of reactive metabolites to cellular proteins play a causative role. Studies were initiated to determine whether nevirapine undergoes cytochrome P450 (P450)-mediated bioactivation in human liver microsomes to electrophilic intermediates. Liquid chromatography-tandem mass spectrometry analysis of incubations containing nevirapine and NADPH-supplemented microsomes in the presence of glutathione (GSH) revealed the formation of a GSH conjugate derived from the addition of the sulfydryl nucleophile to nevirapine. No other GSH conjugates were detected, including conjugates of oxidized metabolites of nevirapine. These findings are consistent with a bioactivation sequence involving initial P450-catalyzed dehydrogenation of the aromatic nucleus with a 4-methyl group in nevirapine to an electrophilic quinone methide intermediate, which is subsequently attacked by glutathione yielding the sulfydryl conjugate. Formation of the nevirapine GSH conjugate was primarily catalyzed by heterologously expressed recombinant CYP3A4 and, to a lesser extent, CYP2D6, CYP2C19, and CYP2A6. In addition, the quinone methide reactive metabolite was a mechanism-based inactivator of CYP3A4, with inactivation parameters K(I) = 31 microM and k(inact) = 0.029 min(-1), respectively. It is proposed that formation of the quinone methide intermediate may represent a rate-limiting step in the initiation of nevirapine-mediated hepatotoxicity.
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PMID:Metabolic activation of nevirapine in human liver microsomes: dehydrogenation and inactivation of cytochrome P450 3A4. 1936 30


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