Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.6 (RNA polymerase)
 34,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The principal goal of the present study was to test the hypothesis that cytokines modulate glucose transport in skeletal muscle by increasing nitric oxide production. Cultured L6 skeletal muscle cells were incubated in the presence of tumour necrosis factor-alpha, interferon-gamma or lipopolysaccharide (LPS) alone or in combination for 24 h. Neither cytokines nor LPS alone induced NO production, as measured by nitrite concentrations in the medium. However, when used in combination, the two cytokines significantly stimulated NO production, and this effect was synergistically enhanced by the presence of LPS. Reverse transcriptase-PCR (RT-PCR) analysis revealed that NO release was associated with the induction of inducible (macrophage-type) NO synthase (iNOS). The increase in iNOS expression was confirmed at the protein level by Western-blot analysis and NADPH/diaphorase histochemical staining. Cytokines and LPS markedly increased basal glucose transport in L6 myocytes. Insulin also stimulated basal glucose transport, but significantly less in cells chronically exposed to cytokines/LPS. The sensitivity of L6 muscle cells to insulin-stimulated glucose transport was also significantly decreased by cytokines/LPS treatment. The NOS inhibitor NG-nitro-l-arginine methyl ester (l-NAME) inhibited nitrite production in cytokine/LPS-treated cells, and this prevented the increase in basal glucose transport and restored muscle cell responsiveness to insulin. Cytokines/LPS exposure significantly increased GLUT1 transporter protein levels but decreased GLUT4 expression in L6 cells. l-NAME treatment prevented the increase in GLUT1 protein content but failed to restore GLUT4 transporter levels. These results demonstrate that cytokines and LPS affect glucose transport and insulin action by inducing iNOS expression and NO production in skeletal muscle cells. The data further indicate that cytokines and LPS increase the expression of the GLUT1 transporter protein by an NO-dependent mechanism.
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PMID:Cytokines modulate glucose transport in skeletal muscle by inducing the expression of inducible nitric oxide synthase. 923 Jan 32

The endometrial secretory phase is characterized by stromal oedema, a premenstrual increase in stromal macrophages and an increased cytokine production as menstruation approaches. Nitric oxide (NO) is a mediator of vasodilatation and cytotoxicity which is synthesized from L-arginine by NO synthases (NOS). These enzymes are either constitutively expressed or induced by lipopolysaccharides and/or cytokines. The presence and function of the inducible isoform of NOS (iNOS) in normal human endometrium has not been fully elucidated until recently. Frozen tissue sections taken from 22 women who underwent hysterectomy and adnexectomy for benign disease were immunostained with antibodies raised against the different NOS isoforms to investigate the presence of NOS in human endometrium. iNOS stained positive in the glandular epithelial cells of the secretory endometrium. Staining was either weak or absent in the proliferative and inactive endometrium, as well as in the oviduct and the glandular epithelium of the endocervix. The stroma remained uniformly negative. Immunoreactivity for endothelial constitutive NOS (eNOS) was confined exclusively to endothelial cells. Furthermore, epithelial cells from endometrium, oviduct and endocervix and all endothelial cells showed positive staining for reduced nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase, which is a histochemical marker for NOS activity. Reverse transcriptase polymerase chain reaction (RT-PCR) was performed in order to assess the presence of NOS mRNA. Abundant expression of iNOS mRNA was detected in the secretory phase endometrium only. The strong expression of inducible NO synthase in human secretory phase endometrium suggests that the increased production of NO, probably induced by cytokines, may be relevant to the process of menstruation.
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PMID:Induction of inducible nitric oxide synthase expression in human secretory endometrium. 955 53

Oltipraz, a promising cancer chemopreventive agent, has been recognized as a monofunctional inducer selectively activating phase II carcinogen-detoxifying enzymes via the antioxidant responsive element (ARE). However, we report here that oltipraz also induces rat glutathione S-transferase A5 (GSTA5), a potent phase II detoxifying enzyme, by means of the xenobiotic responsive element (XRE). Although an ARE sequence exists in the 5' upstream of the rGSTA5 gene, this cis-acting regulatory element loses its responsiveness to oltipraz treatment because of extensive mutations in its distal-half site. Our data indicate that a XRE sequence, located downstream of the transcription initiation site of the gene, is another oltipraz-responsive element. Electrophoretic mobility shift assay showed that oltipraz steadily induces XRE-aryl hydrocarbon receptor (AhR) binding, which can be blocked specifically by excess XRE oligonucleotides or by AhR antibody. By cloning different XREs into the pGL3-promoter vector, we found that oltipraz can activate XRE enhancers from several phase II drug metabolism enzymes, including rGSTA5, rGSTA2, NAD(P)H:quinone reductase, and it also activates XRE from the phase I metabolism enzyme CYP1A1. Oltipraz's effect on XRE is AhR-dependent and is independent of the presence of active CYP1A1. Reverse transcriptase-polymerase chain reaction experiments revealed that oltipraz induces gene expression of both phase I and II drug-metabolizing enzymes in rat hepatoma cells. Thus, we conclude that, like ARE, the XRE pathway constitutes an important part of the molecular mechanism contributing to oltipraz-induced expression of the phase II metabolism enzymes. Oltipraz is a bifunctional inducer, modulating both phase I and II drug-metabolizing enzymes to enhance carcinogen detoxification.
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PMID:Oltipraz is a bifunctional inducer activating both phase I and phase II drug-metabolizing enzymes via the xenobiotic responsive element. 1286 39

The complexity of the plastid transcriptional apparatus (two or three different RNA polymerases and numerous regulatory proteins) makes it very difficult to attribute specific function(s) to its individual components. We have characterized an Arabidopsis T-DNA insertion line disrupting the nuclear gene coding for one of the six plastid sigma factors (SIG4) that regulate the activity of the plastid-encoded RNA polymerase PEP. This mutant shows a specific diminution of transcription of the plastid ndhF gene, coding for a subunit of the plastid NDH [NAD(P)H dehydrogenase] complex. The absence of another NDH subunit, i.e. NDHH, and the absence of a chlorophyll fluorescence transient previously attributed to the activity of the plastid NDH complex indicate a strong down-regulation of NDH activity in the mutant plants. Results suggest that plastid NDH activity is regulated on the transcriptional level by an ndhF-specific plastid sigma factor, SIG4.
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PMID:Specific function of a plastid sigma factor for ndhF gene transcription. 1624 85

Secondary brain injury plays a pivotal role in the outcome of patients suffering from traumatic brain injury (TBI). The mechanisms underlying secondary brain injury are complex and interrelated. Previous studies focused on one of these mechanisms have been proved to be ineffective in clinical practice. Therefore, a target, which can interrupt multi-mechanisms underlying TBI, is desirable. Nrf2-ARE pathway has been proved to be the key regulator in reducing oxidative stress, inflammatory damage and accumulation of toxic metabolites, which are all involved in TBI. However, whether Nrf2-ARE pathway is activated after TBI has not been studied. In the present study, the nuclear Nrf2 protein level was detected by Western blot, and the mRNA levels of heme oxygenase-1 (HO-1) and NAD(P)H: quinone oxidoreductase-1 (NQO1), two Nrf2-regulated gene products, were determined using reverse-transcriptase polymerase chain reaction (RT-PCR) 24h after TBI. Furthermore, we also localized the expression of Nrf2 and HO-1 using immunohistochemical study. After TBI, the nuclear Nrf2 protein level was significantly increased, and the mRNA levels of both HO-1 and NQO1 were also up regulated. Moreover, both Nrf2 and HO-1 were localized in the same types of cells. According to these results, it could be postulated that Nrf2-ARE pathway was activated in brain after TBI.
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PMID:Activation of Nrf2-ARE pathway in brain after traumatic brain injury. 1816 15

The plastid genome (plastome) of heterotrophic plants like mycoheterotrophs and parasites shows massive gene losses in consequence to the relaxation of functional constraints on photosynthesis. To understand the patterns of this convergent plastome reduction syndrome in heterotrophic plants, we studied 12 closely related orchids of three different lifeforms from the tribe Neottieae (Orchidaceae). We employ a comparative genomics approach to examine structural and selectional changes in plastomes within Neottieae. Both leafy and leafless heterotrophic species have functionally reduced plastid genome. Our analyses show that genes for the NAD(P)H dehydrogenase complex, the photosystems, and the RNA polymerase have been lost functionally multiple times independently. The physical reduction proceeds in a highly lineage-specific manner, accompanied by structural reconfigurations such as inversions or modifications of the large inverted repeats. Despite significant but minor selectional changes, all retained genes continue to evolve under purifying selection. All leafless Neottia species, including both visibly green and nongreen members, are fully mycoheterotrophic, likely evolved from leafy and partially mycoheterotrophic species. The plastomes of Neottieae span many stages of plastome degradation, including the longest plastome of a mycoheterotroph, providing invaluable insights into the mechanisms of plastome evolution along the transition from autotrophy to full mycoheterotrophy.
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PMID:Lineage-Specific Reductions of Plastid Genomes in an Orchid Tribe with Partially and Fully Mycoheterotrophic Species. 2741 9