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

Expression or possession of catalase gene may interfere with the iNOS/NO pathway in mycobacteria, hence altering their capacity to survive within macrophages. Therefore, strains of M. smegmatis with an inactive catalase-peroxidase gene (KatG), or into which the KatG gene of Mycobacterium tuberculosis had been transfected, were used to study the influence of catalase on nitric oxide (NO) production and mycobacterial survival within infected murine 1774 macrophages. High levels of nitrite (40-70 nM) were detected in IFN-gamma and LPS activated, infected murine cell culture supernatants, however, NO2- titres produced by infected murine cells did not differ between various catalase phenotype strains. Similarly, no significant difference in mycobacterial killing was also observed among the five strains of M. smegmatis tested over a 3 day infection period.
Biochem Mol Biol Int 1997 Jun
PMID:Influence of Mycobacterium tuberculosis catalase gene (KatG) expression on nitric oxide production and the intracellular growth of transfected Mycobacterium smegmatis strains within murine macrophages. 919 93

Pretreatment with monophosphoryl lipid A (MLA) can pharmacologically mimic the second window of ischemic preconditioning (SWOP) to protect the heart from prolonged ischemia and reperfusion injury. Based on the delayed time course for development of MLA associated cardioprotection, this study was designed to test if MLA's cardioprotective effect is mediated by signalling through production of inducible nitric oxide synthase (iNOS), a proposed effector of SWOP. Rabbits were assigned to one of four groups: (1) vehicle control; (2) MLA: (3) vehicle+aminoguanidine (AMG) control; or (4) MLA+AMG. Monophosphoryl lipid A (35 micrograms/kg) or vehicle was given intravenously 24 h before ischemia. The selective iNOS inhibitor AMG (300 mg/ kg) was injected subcutaneously 1 h before ischemia. All rabbits experienced 30 min coronary artery occlusion followed by 3 h of reperfusion. Infarct size was measured by triphenyltetrazolium chloride (TTC) staining. followed by 3 h of reperfusion. Infarct size was measured by triphenyltetrazolium chloride (TTC) staining. Myeloperoxidase activity, an index of neutrophil infiltration, was also quantified in heart tissue collected from the post-ischemic viable border zone surrounding the infarct area. MLA pretreatment significantly reduced infarct size and neutrophil infiltration in rabbit hearts compared to control (P < 0.05). Inhibition of iNOS activity by AMG abolished the infarct size reductive effect of MLA. Aminoguanidine also blocked the ability of MLA to significantly reduce neutrophil infiltration. Although measurement of iNOS activity did not show induction of the enzyme in normal myocardial tissue 24 h after MLA pretreatment, an increase in iNOS activity in ischemic tissue relative to non-ischemic tissue was found after either 15 or 30 min of coronary occlusion in MLA treated rabbits. These results suggest that MLA pretreatment may enhance iNOS enzyme activity by MLA during ischemia which may be responsible for the observed cardioprotection.
J Mol Cell Cardiol 1997 Jun
PMID:Role of inducible nitric oxide synthase in pharmacological "preconditioning" with monophosphoryl lipid A. 922 Mar 42

Immunocytochemistry was used to localize endothelial (eNOS) and inducible (iNOS) nitric oxide synthase in human uterine tissues collected at various stages of the menstrual cycle, after exposure to exogenous progestagens, and in early pregnancy. Endothelial NOS-like immunoreactivity was detected in all specimens in endothelial cells lining blood vessels in the myometrium and endometrium, and in endometrial glandular epithelial cells. Inducible NOS-like immunoreactivity was also demonstrated in glandular epithelial cells. For both eNOS and iNOS there was considerable variation in the intensity of epithelial cell staining between samples, which was not related to the stage of the menstrual cycle at which the tissue was collected. Messenger RNA for eNOS and iNOS was detected by reverse transcription-polymerase chain reaction (RT-PCR) using total RNA purified from isolated endometrial gland fragments. Immunoreactivity for eNOS and iNOS was not present in endometrial stroma throughout the menstrual cycle, but iNOS-like immunoreactivity was seen in decidualized stromal cells both following treatment with exogenous progestagen (intrauterine L-norgestrel) and in tissues obtained in the first trimester of pregnancy. The detection of protein and mRNA for eNOS and iNOS in normal human endometrium suggests that NO may play a role in the local control of endometrial function.
Mol Hum Reprod 1997 Jan
PMID:Expression of endothelial and inducible nitric oxide synthase in non-pregnant and decidualized human endometrium. 923 10

In addition to left ventricular pump failure and low cardiac output, structural and metabolic alterations of skeletal muscle are thought to contribute to exercise intolerance seen in patients with CHF. Studies using cardiac myocytes have implicated nitric oxide elaborated by inducible nitric oxide synthase (iNOS) as a potential agent associated with the genesis of dilated cardiomyopathy. The present study was designed to locate iNOS in the working skeletal muscle of patients with congestive heart failure. Specific antibodies were used to detect iNOS by immunohistochemistry in skeletal muscle biopsies (m. vastus lateralis) of 37 patients with left ventricular pump failure and 8 normal controls. The expression was restricted to skeletal muscle myocytes and was increased five- to ninefold in patients with chronic heart failure. There was no statistically significant difference in iNOS expression between patients with dilated cardiomyopathy and those with ischemic cardiomyopathy. The finding of a locally increased expression of iNOS and the experimental evidence that NO attenuates the contractile performance of the skeletal muscle suggest that the expression of iNOS may be responsible for the exercise intolerance seen in patients with chronic heart failure.
Biochem Mol Med 1997 Aug
PMID:Increased inducible nitric oxide synthase in skeletal muscle biopsies from patients with chronic heart failure. 925 80

Nitric oxide synthases (NOS) convert L-arginine to nitric oxide in the presence of tetrahydrobiopterin (BH4). Two constitutive isoforms of NOS exist in normal skeletal muscle fibers, however, the existence of a third, the inducible isoform (iNOS), has never been detected in these fibers in vivo. Therefore, we assessed the influence of in vivo endotoxemia on skeletal muscle expression of constitutive and inducible NOS isoforms and GTP cyclohydrolase I, the rate limiting enzyme of BH4 synthesis. Two groups of rats were infused i.p. either with E. coli endotoxin (20 mg/kg, LPS group) or saline (saline group). Animals were killed 6 h later and the ventilatory and limb muscles were quickly frozen. Endotoxin infusion elicited a significant rise in NOS activity of the diaphragm, intercostal, soleus and gastrocnemius muscles. Reverse transcription-polymerase chain reaction (RT-PCR) on muscle total RNA detected very low expression of iNOS and GTP cyclohydrolase I mRNA in the saline group, but significant upregulation of both enzymes was found in the ventilatory and limb muscles of the LPS group. Immunoblotting detected no iNOS protein in the saline group but a significant iNOS protein expression was found in the diaphragm, intercostal and soleus muscles and to a lesser extent, in the gastrocnemius of the LPS group. Endotoxemia was also associated with increased protein expression of constitutive NOS isoforms mainly in the diaphragm and to lesser extent in the intercostal, gastrocnemius and soleus muscles. We conclude that in vivo exposure to endotoxin leads to differential induction of both iNOS and GTP cyclohydrolase I in the ventilatory and limb muscles.
Am J Respir Cell Mol Biol 1997 Aug
PMID:Expression of nitric oxide synthases and GTP cyclohydrolase I in the ventilatory and limb muscles during endotoxemia. 927 5

This study demonstrates that exposure of primary rat hepatocytes or mouse BNL Cl.2 liver cell line to ethanol causes potentiation of tumor necrosis factor-alpha (TNF-alpha)- and lipopolysaccharide (LPS)-stimulated nitrite accumulation. The potentiating effect of ethanol (0.02-2 mM) appears to be time and concentration dependent. Consistent with nitrite production, the amount of inducible nitric oxide synthase (iNOS) mRNA and protein is initially detected at 4 hr after treatment with TNF-alpha/LPS/ethanol. Furthermore, the capability of these agents to induce iNOS expression is primarily determined by the age of the animals. Interestingly, antioxidants such as N-acetylcysteine (NAC), ascorbic acid, or alpha-tocopherol fail to inhibit TNF-alpha/LPS/ethanol-induced increase in iNOS protein. In addition, several kinase inhibitors, including staurosporine, genistein, curcumin, and herbimycin A, were used to examine their effects on this induction. Among them, only herbimycin A potently inhibits the accumulation of nitrite and iNOS expression. In vitro kinase assay verifies that Src tyrosine kinase is rapidly activated with a peak at 1 hr after treatment with TNF-alpha/LPS/ethanol but is not activated by these agents singly or doubly. As expected, herbimycin A can block Src kinase activity under circumstances in which iNOS expression is also inhibited. However, our results do not indicate that the mitogen-activated protein kinase is activated after treatment with these agents. The study results suggest that Src tyrosine kinase plays a prominent role in transducing the signal to induce iNOS expression in hepatocytes treated with TNF-alpha/LPS/ethanol.
Mol Pharmacol 1997 Sep
PMID:The role of Src kinase in the potentiation by ethanol of cytokine- and endotoxin-mediated nitric oxide synthase expression in rat hepatocytes. 928 16

The overall goal of this study was to determine if activation of the nitric oxide synthetic pathway suppressed basal ventricular performance and the responsiveness to beta-adrenergic stimulation characteristic of cardiac function in the 8-week streptozotocin (60 mg/kg, i.v.) diabetic (STZ-Db) rat. Left ventricular performance was measured in isolated working hearts, before and at the peak response to 0.8 microM dobutamine, in the absence or presence of NG-nitro-L-arginine methyl ester (L-NAME, 1 mM), a non-selective inhibitor of nitric oxide synthase (NOS). Ventricular performance was suppressed in the STZ-Db heart under basal (decreased heart rate, cardiac output, aortic flow -dP/dt) and dobutamine-stimulated (diminished rise in +dP/dt and maximum systolic pressure) conditions. L-NAME had minimal effects on basal or dobutamine-stimulated ventricular performance in control hearts. In contrast, L-NAME infusion in hearts from STZ-Db returned the depressed heart rate to control values, which was correlated with an increase in aortic flow. In addition, the dobutamine-stimulated rise in maximum systolic pressure and +dP/dt were similar in the control and STZ-Db rats in the presence of l-NAME. Western blot analysis detected the presence of inducible nitric oxide synthase (NOS) and a significant (P<0.001) increase in the constitutive NOS in ventricular myocytes from STZ-Db rats. These data suggest that an increased production of nitric oxide by NOS in ventricular myocytes from STZ-Db animals suppressed basal ventricular performance and the responsiveness to beta-adrenergic stimulation in diabetic hearts.
J Mol Cell Cardiol 1997 Sep
PMID:Inhibition of nitric oxide synthase by L-NAME improves ventricular performance in streptozotocin-diabetic rats. 929 63

Bio-Normalizer, a natural health food supplement prepared from Carica papaya and some other medicinal plants was investigated to determine its effects on cellular nitric oxide (nitrogen monoxide, NO) production and inducible nitric oxide synthase (iNOS) expression. Bio-Normalizer upregulated interferon (IFN)-gamma-induced NO production by macrophages in a dose-dependent manner. Such an effect of Bio-Normalizer on NO production was not due to changes in the activity of iNOS. Reverse transcription-polymerase chain reaction analysis revealed that the levels of iNOS mRNA were augmented by treatment of the cells with Bio-Normalizer and IFN-gamma. The ability of Bio-Normalizer to augment IFN-gamma-induced iNOS mRNA expression was independent of any changes on the mRNA stability. Treatment of cells with Bio-Normalizer alone did not affect NO production by macrophages. Tumor necrosis factor-alpha and interleukin-1 beta are involved in the induction of iNOS gene as well as the immune system. Bio-Normalizer augmented the mRNA expression of these cytokines in the presence of IFN-gamma. This suggests that Bio-Normalizer is not directly involved in the expression of iNOS, but shows synergistic interaction with IFN-gamma to induce NO synthesis.
Biochem Mol Biol Int 1997 Sep
PMID:Bio-normalizer modulates interferon-gamma-induced nitric oxide production in the mouse macrophage cell line RAW 264.7. 931 92

Nitric oxide (NO) is an important mediator of inflammatory reactions and may contribute to the lung inflammation in allergic pulmonary diseases. To assess the role of NO in pulmonary inflammation, we studied the effect of four nitric oxide synthase (NOS) inhibitors, N-nitro-L-arginine methyl ester (L-NAME), aminoguanidine, N(G)-monomethyl-L-arginine (NMMA) and L-N6-(1-Iminoethyl) lysine (L-NIL), on the influx of eosinophils into the bronchoalveolar lavage (BAL) fluid and lung tissue of antigen-challenged allergic mice. We also analyzed lung tissues for the presence of steady state mRNA for inducible nitric oxide synthase (iNOS) and iNOS protein. Furthermore, BAL fluid and serum were analyzed for their nitrite content. B6D2F1/J mice were sensitized to ovalbumin (OVA) and challenged with aerosolized OVA. The NOS inhibitors were given 0.5 h before and 4 h after the antigen challenge. OVA challenge induced a marked eosinophilia in the BAL fluid and lung tissue 24 h after challenge. The OVA-induced pulmonary eosinophilia was significantly reduced by L-NAME (10 and 50 mg/kg, intraperitoneally [i.p.]). The inactive isomer, D-NAME (50 mg/kg, i.p.) had no effect. When mice were treated with L-NAME (20 mg/kg, i.p.) and an excess of NOS substrate, L-arginine (200 mg/kg, i.p.), the OVA-induced pulmonary eosinophilia was restored. Treatment with aminoguanidine (0.4-50 mg/kg, i.p.) also reduced the pulmonary eosinophilia. Treatment with NMMA (2-50 mg/kg, i.p.) partially reduced the eosinophilia, but L-NIL (10-50 mg/kg, i.p.), a selective iNOS inhibitor, had no effect. L-NAME had no effect on the reduction of eosinophils in the bone marrow following OVA challenge to sensitized mice. OVA challenge to sensitized mice had no effect on iNOS protein expression or iNOS mRNA in the lungs or on the levels of nitrite in the BAL fluid. These results suggest that NO is involved in the development of pulmonary eosinophilia in allergic mice. The NO contributing to the eosinophilia is not generated through the activity of iNOS nor does NO contribute to the efflux of eosinophils from the bone marrow in response to antigen challenge. It is speculated that after antigen challenge, the localized production of NO, possibly from pulmonary vascular endothelial cells, is involved in the extravasation of eosinophils from the circulation into the lung tissue.
Am J Respir Cell Mol Biol 1997 Oct
PMID:Role of nitric oxide on eosinophilic lung inflammation in allergic mice. 937 18

Previous studies have suggested that both nitric oxide (NO) and carbon monoxide (CO) are important modulators of the inflammatory response, while more recent data have implicated both gases as regulators of hypothalamic neuroendocrine function, particularly the hypothalamo-pituitary-adrenal axis. We have, therefore, investigated the modulation of the transcripts for the synthetic enzymes for both NO and CO following the intraperitoneal administration of lipopolysaccharide, serotype B5 055, over the course of 24 h. The mRNA for type I or neuronal nitric oxide synthase (nNOS), and type II or inducible (iNOS), and heme oxygenase1 ('inducible') and heme oxygenase2 ('constitutive'), were reverse transcribed to cDNA, amplified by the polymerase chain reaction, and then quantified using a co-amplified internal standard, beta-actin. This allowed for assessment of relative changes in transcript concentration. In addition, these were compared to changes in expression of the cytokine, IL-1beta. Finally, absolute levels of the synthetic enzyme transcripts were assessed by means of co-amplification in the presence of varying amounts of mutant templates in a competitive PCR reaction. Our data revealed rapid induction of IL-1beta, iNOS and HO1 in the liver, returning to baseline at 24 h. In the hypothalamus, all transcripts were present under basal conditions, but only IL-1beta and iNOS were induced by the LPS. We conclude that hypothalamic IL-1beta and iNOS can be induced by a non-lethal dose of endotoxin, and are, thus, in a position to mediate certain of the neuroendocrine consequences to inflammatory stress.
Brain Res Mol Brain Res 1997 Oct 03
PMID:Induction of nitric oxide synthase and interleukin-1beta, but not heme oxygenase, messenger RNA in rat brain following peripheral administration of endotoxin. 938 83


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