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

Insulin-like growth factors I and II (IGF I and II) are polypeptides with both growth-promoting and insulin-like metabolic effects. Immunoreactive IGF I is present in the retina and both IGF I and II are present in vitreal fluid. The type I and type II IGF receptors are also localized within the neural retina. The presence of IGFs and IGF receptors within the eye suggests a possible growth-promoting effect of IGFs on ocular tissues. IGF may enter the eye from the blood or, alternatively, arise from an ocular cell type which synthesizes and secretes IGF. IGF I and II mRNA synthesis in scleral cells and IGF I synthesis in rat retina suggests endogenous IGF production in the eye. We hypothesized that IGFs and IGF receptors are synthesized by one ocular cell type, the retinal pigment-epithelium (RPE). As a first step in studying IGF production by the RPE, we analyzed expression of the IGF and IGF receptor genes by cultured human RPE cells. Using Northern analysis, RNase protection and reverse-transcriptase polymerase chain reaction (RT-PCR), we found that cultured RPE cells synthesize mRNA for IGF I and the type I and type II IGF receptors.
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PMID:Gene expression of the insulin-like growth factors and their receptors in cultured human retinal pigment epithelial cells. 137 66

The influence of Insulin-like Growth Factor I (IGF-I) on some metabolic functions of Sertoli cells from peripubertal rats was investigated. Sertoli cells were isolated from the testes of 24-day-old animals and cultured at 32 degrees C in Eagle's MEM with or without 1 nM IGF-I. Sertoli cells cultured in the presence of IGF-I showed increased nuclear RNA polymerase activity (+80%) and augmented protein synthesis (+50%).
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PMID:[Effect of insulin-like growth factor I (IGF-I) on Sertoli cell metabolism in the pubescent rat]. 151 Aug 32

Actinomycin D, at a concentration that inhibits cellular ribonucleic acid (RNA) synthesis, inhibited the production of foot-and-mouth disease virus-induced RNA polymerase in baby hamster kidney cells. Inhibition was proportional to exposure time and reached 85% when actinomycin D was added 90 min before infection. Polymerase production was inhibited to the same extent in growth and minimal media, and the kinetics of its appearance were slightly different than in untreated cells. Enzyme preparations from actinomycin-treated cells having one-third to one-tenth the activity of untreated samples gave products with RNA profiles similar to those of controls. The 37S viral peak, 20S ribonuclease-resistant peak, and 26 to 28S peaks were present in all cases. Actinomycin D did not consistently inhibit virus production in either medium. Insulin did not prevent the actinomycin induced inhibition of polymerase and virus production from occurring.
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PMID:Effect of actinomycin D on virus-induced ribonucleic acid polymerase formation in foot-and-mouth disease virus-infected baby hamster kidney cells. 431 46

After the addition of insulin to monolayers of chick fibroblasts previously incubated in serum-free medium, the rates of protein and RNA synthesis increase continuously during the first 8-10 h. Little stimulation of DNA synthesis or mitosis results with the addition of insulin alone in contrast to the addition of fresh serum which stimulates both markedly. The stimulation in RNA synthesis does not result from expansion of the nucleotide pool but is correlated with increases in RNA polymerase activity. All major classes of RNA are stimulated; processing of preribosomal RNA to 28S and 18S and the association of this mature RNA with ribosomes appear to occur normally. The kinetics of stimulation of 5S RNA differ from those of the synthesis of 4S and of ribosomal RNA. Insulin and serum appear to affect the synthesis or stability of certain transcripts differentially.
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PMID:Stimulation by insulin of RNA synthesis in chick fibroblasts. 485 94

Insulin and dexamethasone greatly stimulate the incorporation of 3H-orotic acid into RNA. Such a stimulation is associated to an increase in the uptake of the labelled precursor into the acid soluble fraction as well as in the the specific radioactivity of the nucleoside plus nucleotide pool suggesting that hormone supplementation does not affect RNA synthesis by cultured cells. The lack of effect of insulin and dexamethasone on the level of total RNA polymerase activity in nuclei isolated from cultured hepatocytes is in line with this assumption. The hormone stimulated uptake of orotic acid is dependent on protein synthesis since it is completely abolished by cycloheximide.
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PMID:Hormonal stimulation of 3H-orotic acid incorporation into RNA by serum-free cultured hepatocytes. 619 40

Insulin-like growth factor (IGF-I) is associated with autocrine and paracrine stimulation for cell growth and development of brain tumor cells. The function of IGF-I in the brain metastatic variant of human lung cancer cells is investigated. The cells used here were derived in vivo with intracarotid injection of human non-small cell lung carcinoma NCI-H226. The tumor was developed as a cultured cell line, H226Br. Unlike the parental cells, H226Br was tumorigenic in nu/nu nude mice. Reverse transcriptase-polymerase chain reaction showed that IGF-I transcript of H226Br is increased compared to that of parental cells. The amount of IGF-I secreted in cultured medium of H226Br is higher than that of cultured parental cells. The IGF-I receptor-specific antibody, alpha IR3, inhibits H226Br growth in serum-free culture. The results established that IGF-I is an autocrine growth regulator for human non-small cell lung cancer cells that progressed to brain.
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PMID:Insulin-like growth factor-I is an autocrine regulator for the brain metastatic variant of a human non-small cell lung cell line. 763 43

Cholecystokinin (CCK) has been suggested to modulate insulin output. We have shown that Otsuka Long-Evans Tokushima Fatty (OLETF) rats show little or no expression of the CCK-A receptor gene in the pancreas. We examined whether the CCK-A and CCK-B receptor genes are expressed in the islets and the role of CCK-A receptor in insulin secretion. Gene expressions of CCK receptors were determined by the reverse-transcriptase polymerase chain reaction (RT-PCR) followed by Southern blot hybridization and Northern transfer analysis using LETO rats as controls. Pancreatic endocrine function was examined in perfusion (exogenous CCK stimulation) and meal ingestion (endogenous CCK stimulation) studies. CCK-A receptor mRNA was detected in the islets of LETO rats but not OLETF rats. Expression of the CCK-B receptor gene was detected in both strains by RT-PCR. Insulin secretion was impaired in OLETF rats, but the insulin contents of OLETF and LETO rats were not different. No abnormalities were detected histologically in either strain. These results suggest that the occurrence of pancreatic endocrine dysfunction in OLETF rats may be due to a defect in expression of the CCK-A receptor gene, not to insulin deficiency.
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PMID:Pancreatic endocrine dysfunction in rats not expressing the cholecystokinin-A receptor. 883 Mar 28

Insulin-response glucose transporter GLUT4 is a member of the glucose transporter family (GLUT) and is present exclusively in muscle and adipose tissue. It is a target of insulin action in humans and rodents. To clarify the molecular structure of bovine GLUT4, its GLUT4 cDNA was cloned by the RT-PCR method. Several cDNA clones corresponding to the different regions of GLUT4 were obtained by amplifying reverse-transcriptase products of RNA extracted from Holstein cattle skeletal muscle. Nucleotide sequence analysis of the cDNA clones revealed that bovine GLUT4 cDNA was composed of 2,656 base pairs with a coding region for a 509 amino acid protein. The deduced amino acid sequence was 64% and 92% identical with bovine GLUT1 (GLUT ubiquitously expressed in all tissues) and rat GLUT4, respectively. Although the amino acid sequence of the GLUT4 COOH-terminal region is highly conserved among the species so far reported, one amino acid (Asp) of the region was replaced by His in bovine GLUT4. The tissue distribution of GLUT4 was also examined by Northern blot analysis using a probe prepared from the bovine cDNA. GLUT4 mRNA was detected in skeletal muscle, heart, and adipose tissue, but not in liver, kidney, lung, brain, or spleen. Such a distribution is essentially the same as in humans and rodents, suggesting that GLUT4 is an insulin-responsive glucose transporter in cattle.
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PMID:Molecular cloning and mRNA expression of the bovine insulin-responsive glucose transporter (GLUT4). 902 64

Insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) is a polypeptide that forms a ternary complex with IGFs and an acid-labile subunit. The hormonal regulation of the components of this complex is highly controversial, and both IGF-I and GH have been shown to mediate the expression/synthesis of IGFBP-3. This study investigates the regulation of IGFBP-3 protein, measured by RIA and Western ligand blot, and messenger RNA (mRNA) expression, measured by Northern analysis and reverse transcriptase-PCR, in SKHEP-1 human hepatocarcinoma cells. SKHEP-1 cells significantly increased the IGFBP-3 concentrations in conditioned medium (CM) when treated with GH (0.1-10 ng/ml), IGF-I (1-100 ng/ml), or Des(1-3)-IGF-I (1-100 ng/ml) in a dose-dependent manner (>3-fold). The increase in IGFBP-3 protein concentrations in CM was accompanied by a corresponding increase in IGFBP-3 mRNA levels. Interestingly, time-course studies showed that the GH-induced increase in IGFBP-3 mRNA preceded the IGF-I-induced increase (6 h for GH-induced IGFBP-3 mRNA; 12 h for IGF-I-induced IGFBP-3 mRNA). The half-life of IGFBP-3 mRNA was evaluated after transcriptional arrest by treatment with a RNA polymerase II inhibitor (5,6-dichloro-1beta-D-ribofuranosylbenzimidazole), and was found to be 14-18 h and unaltered by GH or IGF-I treatment. The induction of IGFBP-3 by GH was not due to the indirect action of locally synthesized IGF-I, because 1) no immunoreactive IGF-I was detected in the CM of control or GH-treated cells; 2) Northern blots revealed no IGF-I mRNA expression in SKHEP-1 cells; 3) reverse transcriptase-PCR did not detect any expression of the IGF-I gene; and 4) time-course studies showed an earlier increase in IGFBP-3 mRNA after GH treatment than after IGF-I treatment. Thus, the results obtained in this study are consistent with an IGF-I-independent regulation of IGFBP-3 gene expression by GH.
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PMID:Evidence for insulin-like growth factor (IGF)-independent transcriptional regulation of IGF binding protein-3 by growth hormone in SKHEP-1 human hepatocarcinoma cells. 907 3

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


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