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

---

Query: EC:2.5.1.18 (glutathione S-transferase)
22,582 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Many individuals with cardiovascular diseases undergo physical conditioning with or without medication. Therefore, this study investigated the interaction of exercise training and chronic nitroglycerin treatment on blood pressure (BP) and changes in cardiac nitric oxide (NO) and antioxidants in rats. Fisher 344 rats were divided into four groups treated as: (1) sedentary control, (2) exercise training for 8 weeks, (3) nitroglycerin (15 mg/kg, s.c. for 8 weeks), and (4) training+nitroglycerin for 8 weeks. Respiratory exchange ratio (RER), BP, and heart rate (HR) were monitored weekly for 8 weeks. The animals were sacrificed 24 h after last treatments, hearts isolated, and analyzed. Physical conditioning significantly increased RER, cardiac NO levels, and endothelial eNOS protein expression. Training significantly enhanced cardiac glutathione (GSH) levels, GSH/GSSG ratio, and the up-regulation of cardiac copper/zinc-superoxide dismutase (CuZn-SOD), manganese (Mn)-SOD, catalase (CAT), glutathione peroxidase (GSH-Px) activities, and protein expression. Training also caused depletion of cardiac malondialdehyde (MDA) and protein carbonyls with a significant increase in RER without any change in BP and HR. Chronic nitroglycerin administration significantly increased cardiac NO levels and eNOS protein expression. Nitroglycerin administration significantly enhanced cardiac Mn-SOD, CAT, and GST activities, and protein expression with decreased MDA levels and BP. Interaction of training and chronic nitroglycerin treatment increased cardiac NO levels with enhanced eNOS and iNOS protein expressions, GSH/GSSG ratio, and the up-regulation of antioxidant enzymes. This interaction normalized BP and HR and increased RER. The data suggest that the interaction of physical training and chronic nitroglycerin treatment resulted in the maintenance of BP and RER by up-regulating the antioxidants and NO levels and by reducing the oxidative stress in the rat heart.
...
PMID:Interaction of physical training and chronic nitroglycerin treatment on blood pressure, nitric oxide, and oxidants/antioxidants in the rat heart. 1286 Apr 43

The objective of this study is to determine if treatment with the angiogenesis inhibitor TNP-470 results in impairment of oxidative stress, inhibition of nuclear factor kappa B (NF-kappaB) activation and decrease of nitric oxide production in an experimental model of rat hepatocarcinogenesis. Tumour was induced by diethylnitrosamine and promoted by two-thirds hepatectomy plus acetaminofluorene administration. Experiments were carried out at 28 weeks after initiating the treatment. TNP-470 was administered at 30mg/kg, three times per week from 20 to 28 weeks. Carcinomatous tissue growing outside dysplastic nodules and a marked expression of placental glutathione S-transferase were detected in rats with induced carcinogenesis. Liver concentrations of thiobarbituric acid reactive substances, reduced glutathione (GSH) and glutathione disulfide (GSSG) were significantly higher than those of controls and there was a significant increase in the GSSG/GSH ratio. Tumour growth was accompanied by augmented expression of inducible nitric oxide synthase, activation of (NF-kappaB) and proteolysis of IkappaB. All these effects were absent in animals receiving TNP-470. Our results indicate that TNP-470 inhibits oxidative stress, nitric oxide production and NF-kappaB activation induced by experimental hepatocarcinogenesis. These changes would contribute to the beneficial effects of TNP-470 in cancer treatment.
...
PMID:TNP-470 inhibits oxidative stress, nitric oxide production and nuclear factor kappa B activation in a rat model of hepatocellular carcinoma. 1456 44

Interferon regulatory factor-1 (IRF-1) is a transcription factor exhibiting functional diversity because of its ability to activate transcription from promoters of several IRF-1-dependent genes. It is a modular protein, where the overall structure is not essential for function of its individual domains. A comparison of the mouse and human IRF-1 amino acid sequences enabled us to identify a stretch of six amino acids (198-203) within the transactivation domain of mouse IRF-1, 198MQMDII(203) to be different from that of the human IRF-1, 197IPVEVV(202). This indicated a possible functional significance of the six amino acid stretches in the two IRF-1 molecules. The murine IRF-1 sequence at 198-203 (MQMDII) was replaced by IPVEVV. Recombinant wild type mouse IRF-1 with 198MQMDII(203) and its mutant form with 198IPVEVV(203), expressed as GST-IRF-1-fusion proteins, showed similar DNA-binding activity. However, ectopic expression of the wild type and mutant IRF-1 in the human embryonic kidney (HEK-293) cells showed the effect of replacement of this region on expression of a few chromosomal genes that are transcriptionally activated by IRF-1 viz. IFN-beta, iNOS, and COX-2 genes. In our study, expression of wild type IRF-1 activated these genes as judged by RT-PCR but the mutant IRF-1 did not show this effect. Thus, the MQMDII (198-203 a.a.) region of mouse IRF-1 has a functional context in relation to expression of IRF-1-inducible genes.
...
PMID:Replacement of 198MQMDII203 of mouse IRF-1 by 197IPVEVV202 of human IRF-1 abrogates induction of IFN-beta, iNOS, and COX-2 gene expression by IRF-1. 1474 97

Signal transducer and activator of transcription 3 (STAT3) and nuclear factor kappaB (NF-kappaB) are important transcription factors involved in glomerulonephritis and other inflammatory processes, including transcription of the inducible nitric oxide synthase (iNOS) gene. The ability of STAT3 to interact physically with NF-kappaB p65 in glomerular mesangial cells and thereby to inhibit NF-kappaB-mediated transactivation of the iNOS gene was demonstrated previously. STAT3 is a modular protein with several structurally and functionally defined domains. For defining STAT3 domains that interact with NF-kappaB p65, (35)S-labeled proteins that corresponded to each STAT3alpha domain were synthesized, and their ability to bind specifically a GST-NF-kappaB p65 fusion protein in GST pulldown assays was tested. The coiled-coil and DNA-binding domains were specifically retained by GST-NF-kappaB p65, whereas the N-terminal, linker domain, Src homology 2 domain, and transcriptional activation domain failed to interact with NF-kappaB p65. Deletion of the region L(358) through I(369) of the STAT3 DNA-binding domain greatly reduced binding to GST-NF-kappaB p65. Alanine substitution mutations at four highly conserved residues-L(358), N(359), K(363), and V(366)-in this region greatly abrogated the ability of STAT3 to bind NF-kappaB p65. Moreover, in contrast to the transrepression afforded by wild-type STAT3alpha, a STAT3alpha construct harboring these mutations, failed to suppress endogenous NO production and to transrepress iNOS promoter-reporter and kappaB element-reporter constructs in IL-beta-stimulated mesangial cells. These data reveal a novel role for the DNA-binding domain in the physical and functional coupling of STAT3 to NF-kappaB p65 that is important for regulating the transcriptional activity of iNOS and likely other NF-kappaB p65 responsive genes that are important for mesangial cell responses.
...
PMID:The STAT3 DNA-binding domain mediates interaction with NF-kappaB p65 and inducible nitric oxide synthase transrepression in mesangial cells. 1497 60

Oral squamous cell carcinoma is one of the most common human neoplasms, and prevention of this malignancy requires a better understanding of its carcinogenesis process. To this end, we tried to establish an animal model using the human c-Ha-ras proto-oncogene-carrying transgenic (Tg) rats and the carcinogen 4-nitroquinoline 1-oxide (4-NQO). 4-NQO (20 p.p.m.) was administered to Tg and non-Tg rats for 8 weeks in their drinking water, and then the occurrence of tongue carcinogenesis was compared during the experimental period of 22 weeks. In addition, we determined the DNA ploidy in tongue lesions and examined the immunohistochemical expression of five biomarkers such as cyclin D1, glutathione S-transferase placental form, cyclooxygenase (COX)-2, inducible nitric oxide synthase (iNOS) and beta-catenin. Next, the cancer chemopreventive effects of nimesulide, pioglitazone and a synthetic geranylated derivative, which have been reported to be inhibitors of tongue carcinogenesis, were examined in Tg rats treated with 4-NQO. Either during or after treatment with 4-NQO in the drinking water, tongue dysplasia and tumors were observed on the tongues of both Tg and non-Tg rats, with a greater incidence and multiplicity in Tg rats. Histopathologically, squamous cell dysplasia, papilloma and carcinoma with or without invasion were present in the tongue. Immunohistochemistry revealed that expression levels against five biomarkers increase with disease progression, and the changes correlated with those of the DNA ploidy pattern. Interestingly, a strong expression of COX-2, iNOS and beta-catenin was observed on the invasive front of squamous cell carcinomas. A subsequent chemoprevention study using Tg rats showed that the chemicals tested suppressed the occurrence of tongue carcinomas when they were administered after 4-NQO-exposure. These results may thus indicate that our 4-NQO-induced Tg rat tongue carcinogenesis model simulates many aspects of human oral carcinogenesis and it can be applied for an analysis of oral cancer development while also helping to identify potentially effective cancer chemopreventive agents against oral cancer.
...
PMID:An animal model for the rapid induction of tongue neoplasms in human c-Ha-ras proto-oncogene transgenic rats by 4-nitroquinoline 1-oxide: its potential use for preclinical chemoprevention studies. 1621 33

Fish Lateolabrax japonicus were exposed to 0.1 and 1mg/L of anion surfactant sodium dodecylbenzene sulfonate (SDBS) and to 2 and 20 microg/L of benzo[a]pyrene (B[a]P) for 6, 12, and 18 days, with control and solvent control groups. Liver antioxidant enzymes, including superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH), and glutathione S-transferase (GST), were determined; brain acetylcholinesterase (AChE) and liver inducible nitric oxide synthase (iNOS) activities were also measured. The results indicated that (1) L. japonicus avoided oxidative damage through antioxidant systems; (2) SOD, GPx, and GSH were induced, and GST was inhibited and then induced by B[a]P exposure; and (3) CAT, GPx, and AChE were induced while iNOS was inhibited, and GST was induced and then inhibited by SDBS stress in experimental period.
...
PMID:Response of integrated biomarkers of fish (Lateolabrax japonicus) exposed to benzo[a]pyrene and sodium dodecylbenzene sulfonate. 1625 95

Although vitamin B6 has been supposed to have anti-inflammatory effects, the molecular mechanism is not fully understood. To explore the mechanism of anti-inflammatory effects of vitamin B6, we have examined the effect of vitamin B6 on lipopolysaccharide (LPS)-stimulated inflammatory response in RAW 264.7 macrophages. This study demonstrated that vitamin B6 (pyridoxal) pretreatment of RAW cells inhibited LPS-induced expression of iNOS and COX-2 at the mRNA and protein levels. Vitamin B6 inhibited LPS-induced nuclear translocation of the NF-kappaB, the proinflammatory transcription factor, with reduction of the extent of LPS-induced IkappaBalpha degradation in RAW cells. Although vitamin B6 did not affect cellular proteasome activity, in vitro phosphorylation analysis with glutathione S-transferase-fused IkappaBalpha has shown that vitamin B6 suppressed LPS-induced IkappaB kinase activation. Furthermore, we demonstrated that elevating dietary vitamin B6 suppressed NO production in vivo in response to LPS administration. These observations suggest that the anti-inflammatory effect of vitamin B6 is mediated by suppression of NF-kappaB activation.
...
PMID:Vitamin B6 suppresses NF-kappaB activation in LPS-stimulated mouse macrophages. 1627 88

N-acetylcysteine (NAC) and S-methylcysteine (SMC), water soluble organosulfur compounds contained in garlic, were evaluated for chemoprevention of hepatocarcinogenesis after 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) initiation in rats. Intergastric treatment with NAC or SMC five times a week resulted in decreased numbers and areas of preneoplastic, glutathione S-transferase placental form (GST-P) positive foci of the liver in a dose-dependent manner. Moreover, cell proliferation was reduced in GST-P positive foci by NAC and SMC. Insulin-like growth factor I (IGF-I) and inducible nitric oxide synthase (iNOS) mRNA expressions were found downregulated in the liver by NAC. The studies indicate that NAC can serve as a chemopreventive agent for rat hepatocarcinogenesis induced by MeIQx by reducing cell proliferation, which may involve IGF-I and iNOS downregulation.
...
PMID:N-acetylcysteine and S-methylcysteine inhibit MeIQx rat hepatocarcinogenesis in the post-initiation stage. 1633 51

The proliferative inflammatory atrophy (PIA) is considered as a possible precursor of prostate intraepithelial neoplasia (PIN) or prostate cancer (PCa). In this study we assessed quantitatively the expression of AMACR, p63, COX-2, GST and iNOS in serial paraffin-embedded tissue sections obtained after radical prostatectomy of PCa patients (n = 30). The applicability of these markers to distinguish PIA, PIN and PCa was evaluated. We also compared the immunohistochemical expression profiles of AMACR, COX-2 and GST in the luminal and basal cells in lesions of PIN arisen in PIA or PIA alone. Two different patterns of COX-2 expression according to the p63 status of the basal cells were found. This observation gives us grounds to hypothesize that the diverse COX-2 patterns resulted from an initial basal cell damage which subsequently propagated to its luminal secretory cells progeny.
...
PMID:Quantitative immunohistochemical detection of the molecular expression patterns in proliferative inflammatory atrophy. 1717 35

Although studies have shown that administration of testosterone receptor antagonist, flutamide, following trauma-hemorrhage, improves hepatic, cardiovascular, and immune functions, the precise cellular/molecular mechanisms responsible for producing these salutary effects remain largely unknown. To study this, male C3H/HeN mice were subjected to a midline laparotomy and hemorrhagic shock (35+/-5 mmHg for approximately 90 min), followed by resuscitation with Ringer lactate. Flutamide (25 mg/kg) or vehicle was administered subcutaneously at the onset of resuscitation, and animals were killed 2 h thereafter. Hepatic injury was assessed by plasma alpha-glutathione S-transferase concentration, liver myeloperoxidase activity, and nitrotyrosine formation. Hepatic malondialdehyde and 4-hydroxyalkenals (lipid peroxidation indicators), cellular DNA fragmentation, and the expression of inducible nitric oxide synthase and hypoxia-inducible factor-1alpha were also evaluated. Cytokines (TNF-alpha, IL-6) and chemokines (keratinocyte-derived chemokine and monocyte chemoattractant protein-1) levels were determined by cytometric bead array. The results indicate that flutamide administration after trauma-hemorrhage reduced liver injury, which was associated with decreased levels of alpha-glutathione S-transferase, myeloperoxidase activity, nitrotyrosine formation, lipid peroxidation, and cytokines/chemokines (systemic, liver tissue, and intracellular cytokines/chemokines). Cellular apoptosis, hepatocyte hypoxia-inducible factor-1alpha, and inducible nitric oxide synthase expression were also decreased under such conditions. Thus administration of flutamide following trauma-hemorrhage protects against liver injury via reduced inflammation, cellular oxidative stress, and apoptosis.
...
PMID:Flutamide protects against trauma-hemorrhage-induced liver injury via attenuation of the inflammatory response, oxidative stress, and apopotosis. 1853 30


<< Previous 1 2 3 4 5 6 7 Next >>

---