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 reactive nitrogen species, nitric oxide (NO), plays an important role in the pathogenesis of neurodegenerative diseases. The suppression of NO production may be fundamental for survival of neurons. Here, we report that pretreatment of human ramified microglial cells with nearly physiological levels of exogenous NO prevents lipopolysaccharide (LPS)/tumor necrosis factor alpha (TNF alpha)-inducible NO synthesis, because by affecting NF-kappa B activation it inhibits inducible Ca(2+)-independent NO synthase isoform (iNOS) mRNA expression. Using reverse transcriptase polymerase chain reaction, we have found that both NO donor sodium nitroprusside (SNP) and authentic NO solution are able to inhibit LPS/TNF alpha-inducible iNOS gene expression; this effect was reversed by reduced hemoglobin, a trapping agent for NO. The early presence of SNP during LPS/TNF alpha induction is essential for inhibition of iNOS mRNA expression. Furthermore, SNP is capable of inhibiting LPS/TNF alpha-inducible nitrite release, as determined by Griess reaction. Finally, using electrophoretic mobility shift assay, we have shown that SNP inhibits LPS/TNF alpha-elicited NF-kappa B activation. This suggests that inhibition of iNOS gene expression by exogenous NO may be ascribed to a decreased NF-kappa B availability.
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PMID:Induction of nitric oxide synthase mRNA expression. Suppression by exogenous nitric oxide. 759 3

The inducible NO synthase (iNOS) was found to be expressed in pancreatic lesions of adult diabetes-prone BB rats. Pancreatic iNOS mRNA was detected by reverse transcriptase PCR in pancreatic RNA of adult diabetes-prone BB rats but not in normal Wistar rats, young diabetes-prone BB rats without insulitis or in diabetes-resistant BB rats. Immunohistochemistry of pancreatic sections using an iNOS-specific antiserum labeled the pancreas of adult diabetes-prone BB rats but not Wistar rats. Parallel staining for ED1-positive macrophages showed restriction of iNOS expression to areas of islet infiltration by macrophages. In conclusion, the data provide direct evidence for enhanced expression of inducible NO synthase in tissue lesions during the development of autoimmune diabetes.
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PMID:Transcription and translation of inducible nitric oxide synthase in the pancreas of prediabetic BB rats. 768 27

The mechanism for myometrial quiescence during pregnancy is unknown. cGMP plays an integral role in the relaxation of smooth muscle, and nitric oxide (NO) is the most important endogenous activator of soluble guanylate cyclase. The purpose of this study was to determine the effect of gestational age on myometrial cGMP and NO synthase (NOS) activity in the guinea pig. Myometrial cGMP content (measured by RIA) rose slowly until 0.49 (fraction of pregnancy completed) gestation before abruptly increasing to 200 times the non-pregnant control value. It then declined precipitously after 0.87 gestation. Of the known isoenzymes of NOS, the messenger RNAs coding for both endothelial and neuronal NOS could be amplified from the myometrium of pregnant and nonpregnant animals using reverse transcriptase-polymerase chain reaction, but inducible NOS messenger RNA was not found. Myometrial calcium-dependent NOS activity (measured by the conversion of L-[U-14C]arginine to [U-14C]citrulline) declined slowly with advancing gestation (r2 = 0.096; slope = -0.34; P = 0.01), but never differed significantly from the activity in nonpregnant animals [31.1 +/- 11 (term pregnancy) vs. 56.9 +/- 16 (nonpregnant) pmol/min.g; P = NS]. Calcium-independent activity declined shortly after conception, and then rose toward the nonpregnant level (r2 = 0.19; slope = 0.45; P = 0.0009). However, at no time was it significantly different from that in the nonpregnant animal. Pregnancy had no effect on myometrial L-arginine and L-citrulline content. The administration of L-nitro-arginine methyl ester (200 mg/kg) to inhibit NOS dramatically increased blood pressure and reduced fetal renal NOS activity, but had no effect on the myometrial cGMP content. Estradiol (500 micrograms/kg for 5 days) modestly increased cGMP, but in contrast to many tissues in which estradiol increases NOS, it had no effect on myometrial NOS activity. We conclude that pregnancy dramatically increases cGMP by a mechanism independent of NOS. The stimulus remains to be identified. The temporal change in cGMP concentration is consistent with the hypothesis that cGMP mediates myometrial quiescence during pregnancy.
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PMID:Pregnancy increases guanosine 3',5'-monophosphate in the myometrium independent of nitric oxide synthesis. 798 34

Nitric oxide is known to participate in the immune and inflammatory processes. In this study, we investigated the production of nitric oxide (NO) in murine viral myocarditis induced by coxsackievirus B3. The expression of inducible NO synthase (iNOS) mRNA in the heart first appeared on day 4 after virus inoculation and it was detectable for one month by reverse transcriptase-polymerase chain reaction (RT-PCR) methods. iNOS activity which was determined by the conversion of L-[3H]arginine to L-[3H]citrulline was increased on day 4 and revealed its peak on day 8. Immunohistochemistry on day 7 showed increased iNOS staining mainly in infiltrating macrophages and polymorphonuclear leukocytes. Thus, NO is thought to be produced in the heart and play an important role in a murine model of coxsackievirus B3-induced viral myocarditis.
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PMID:Expression of nitric oxide synthase in a murine model of viral myocarditis induced by coxsackievirus B3. 860 80

This study shows that human ramified microglial cells derived from fetal brain primary cultures, are able to produce nitric oxide (NO). In fact, stimulation with Escherichia coli lipopolysaccharide (LPS) (1 microgram ml-1) or tumor necrosis factor alpha (TNF alpha) (500 U ml-1) enhances nitrite release in cell supernatants, as determined by the Griess reaction. A synergistic effect is achieved following treatment with LPS plus TNF alpha, this effect being inhibited by pretreating cells with NOS inhibitor N omega-nitro-L-arginine methyl ester (L-NAME). Using reverse transcriptase-polymerase chain reaction (RT-PCR) and Southern blot analysis, we also found that LPS/TNF alpha produce an increase of inducible NO synthase (iNOS) mRNA expression.
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PMID:Human ramified microglial cells produce nitric oxide upon Escherichia coli lipopolysaccharide and tumor necrosis factor alpha stimulation. 861 65

Nitric oxide (NO) has been implicated as a pathogenic mediator in a variety of central nervous system (CNS) disease states, including the animal model of multiple sclerosis (MS) and experimental allergic encephalomyelitis. We have examined post-mortem brain tissues collected from patients previously diagnosed with MS, as well as tissues collected from the brains of patients dying without neuropathies. Both Northern blot analysis and reverse transcriptase (RT)-driven in situ PCR (RT-in situ PCR) studies demonstrated that inducible NO synthase (iNOS) mRNA was present in the brain tissues from MS patients but was absent in equivalent tissues from normal controls. We have also performed experiments identifying the cell type responsible for iNOS expression by RT-in situ PCR in combination with immunohistochemistry. Concomitantly, we analyzed the tissues for the presence of the NO reaction product nitrotyrosine to demonstrate the presence of a protein nitrosylation adduct. We report here that iNOS mRNA was detectable in the brains of 100% of the CNS tissues from seven MS patients examined but in none of the three normal brains. RT-in situ PCR experiments also demonstrated the presence of iNOS mRNA in the cytoplasm of cells that also expressed the ligand recognized by the Ricinus communis agglutinin 1 (RCA-1), a monocyte/macrophage lineage marker. Additionally, specific labeling of cells was observed when brain tissues from MS patients were exposed to antisera reactive with nitrotyrosine residues but was significantly less plentiful in brain tissue from patients without CNS disease. These results demonstrate that iNOS, one of the enzymes responsible for the production of NO, is expressed at significant levels in the brains of patients with MS and may contribute to the pathology associated with the disease.
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PMID:Activation of the inducible form of nitric oxide synthase in the brains of patients with multiple sclerosis. 861 40

A cytokine-inducible form of nitric oxide synthase (iNOS), capable of producing large quantities of nitric oxide (NO), can be induced in many cell types. We demonstrate that conditioned medium from encephalitogenic myelin basic protein-sensitized lymphoid cells (MBP-CM) induces the expression of iNOS in primary cultures of murine astrocytes in a time- and concentration-dependent manner. iNOS mRNA was detected by reverse transcriptase-polymerase chain reaction (RT-PCR) as early as 3 h post-exposure. Accumulation of nitrite into the astrocyte culture medium, an indirect measure of NO, was measurable 3 h post-exposure, plateaued at 24 h, and was prevented by the simultaneous administration of the NOS inhibitors, L-N(G)-nitroarginine methyl ester, N(G)-nitro-L-arginine or aminoguanidine. Astrocyte expression of iNOS protein, detected by immunohistochemistry and immunoprecipitation/Western blot, was prevented by inhibitors of RNA or protein metabolism, consistent with its dependence on de novo protein synthesis.
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PMID:Murine encephalitogenic lymphoid cells induce nitric oxide synthase in primary astrocytes. 863 63

Nitric oxide is reportedly involved in the regulation of several ovarian processes, yet the isoforms of nitric oxide synthase (NOS) expressed in the ovary are unknown. Our purpose was to identify and localize NOS isoenzymes in the rat ovary and to examine++ if mRNA expression of NOS isoenzymes change after gonadotropin stimulation. Using reverse transcriptase-PCR, we demonstrated that inducible (iNOS) and endothelial (eNOS), but not neuronal, NOS mRNAs are expressed in the ovary. In a gonadotropin-stimulated rat model, unstimulated ovaries had the highest levels of iNOS mRNA as quantified by ribonuclease protection assay. After gonadotropin injection, iNOS mRNA declined to undetectable levels in ovaries containing ovulatory follicles before increasing slighty in ovaries containing copora lutea. In situ hybridization studies localized iNOS to granulosa cells of secondary follicles and small antral follicles. Western blots of unstimulated ovaries demonstrated iNOS protein. In contrast to iNOS, eNOS mRNA levels, determined by quantitative PCR, increased after gonadotropin stimulation and peaked in ovaries containing ovulatory follicles before declining in the luteal phase. eNOS protein was localized to blood vessels in the ovary by immunohistochemistry. We conclude that two isoforms of NOS are expressed in the ovary and the mRNA levels for these isozymes are differentially regulated.
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PMID:Expression and localization of inducible and endothelial nitric oxide synthase in the rat ovary. Effects of gonadotropin stimulation in vivo. 867 39

Since nitric oxide (NO) has been implicated in the pathogenesis of various hyperproliferative and inflammatory diseases, the mRNA expression of constitutive nitric oxide synthase (cNOS) and inducible nitric oxide synthase (iNOS) were investigated in psoriatic skin by reverse transcriptase coupled to the polymerase chain reaction (PCR). The study showed that the mRNA expression of brain nitric oxide synthase (bNOS), one of two isoforms of cNOS, was weak in both psoriatic plaques lesions and uninvolved skin, while mRNA transcripts for the second isoform, endothelial nitric oxide synthase (eNOS), were not detectable using the present method. In contrast, the mRNA expression of iNOS was markedly increased in lesional skin as compared to uninvolved skin. Cultured human keratinocytes exposed to a combination of interleukin-1 beta (IL-1 beta) and tumour necrosis factor-alpha (TNF-alpha) for 4 h, showed strong gene expression of iNOS, while in 24 h, the expression had returned to baseline expression. In summary, the study demonstrates that mRNA for the inducible form of NOS is over-expressed in psoriatic lesions. The cause of this may be the local presence of inflammatory cytokines. These findings imply that iNOS may play an important part in local regulation of NO synthesis in psoriasis and other inflammatory dermatoses.
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PMID:Increased expression of inducible nitric oxide synthase in psoriatic skin and cytokine-stimulated cultured keratinocytes. 903 17

Insulin-dependent diabetes mellitus (IDDM) is an autoimmune disease that is characterized by selective destruction of insulin-secreting beta-cells. Cytokines have been implicated as effector molecules that participate in both islet inflammation and beta-cell destruction during the development of IDDM. In this study, the effects of cytokines on the expression of inducible nitric oxide synthase (iNOS) and inducible cyclooxygenase (COX-2) by human islets were examined. In combination, the cytokines, human recombinant interleukin-1 beta (IL-1 beta), human recombinant tumor necrosis factor-alpha (TNF-alpha), and human recombinant interferon-gamma (IFN-gamma), induce the time-dependent formation of nitrite and prostaglandin E2 (PGE2) by human islets. The nitric oxide synthase inhibitor NG-monomethyl-L-arginine (L-NMMA) completely inhibits cytokine-induced nitrite formation and attenuates PGE2 production by human islets. L-NMMA does not inhibit cytokine-induced expression of COX-2 by human islets, suggesting that nitric oxide may directly activate cyclooxygenase, an effect that has been previously demonstrated for isolated rat islets. This combination of cytokines (IL-1 beta, TNF-alpha, and IFN-gamma) also induces the expression of iNOS mRNA by human islets as demonstrated by both reverse transcriptase-polymerase chain reaction and Northern blot analysis. We further show that the tyrosine kinase inhibitors genistein and herbimycin A prevent IL-1 beta plus IFN-gamma-induced expression of COX-2 and iNOS and the production of PGE2 and nitric oxide by human islets. These results demonstrate that cytokines induce the expression of iNOS and COX-2 by human islets and that cytokine-induced expression of both COX-2 and iNOS by human islets appears to require the activation of a tyrosine kinase(s).
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PMID:Tyrosine kinase inhibitors prevent cytokine-induced expression of iNOS and COX-2 by human islets. 876 39


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