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:3.1.27.5 (RNase)
17,967 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Erectile dysfunction is often associated with problems in vascular perfusion to the erectile components of the penis. In order to better understand the factors that control vascular formation and perfusion in the erectile tissues of the penis, we have begun to characterize the expression of vascular endothelial growth factor (VEGF) in penis tissues. VEGF is one of several polypeptides that have significant angiogenic activity in vitro and in vivo. Extensive characterization of the VEGF gene and its products has shown that several different mature mRNA transcripts exist, originating from alternative splicing of the basic VEGF transcript. These variant transcripts can encode peptides with different biological activities. Penile tissue was obtained from adult rats and from human patients undergoing penile prosthesis implantation. Analysis of the forms of VEGF transcripts was performed using a reverse transcription-polymerase chain reaction technique with primer pairs derived from the first and eighth exon of the VEGF gene. The expression levels of the various isoforms in the rat penis were then quantified using RNase protection assays. Four previously described splice variants of VEGF mRNA (VEGF 120, 144, 164, 188) were detected in rat and human penile tissues. In contrast to what is seen in the rat lung, where the most abundant form of VEGF mRNA is the 188 splice isoform, VEGF 164 is the most abundant transcript detected in the penis. Finally, sequence analysis of numerous VEGF cDNA clones obtained from the rat penis demonstrated the presence of a previously undescribed VEGF splice variant that could give rise to a protein of 110 amino acid residues (VEGF 110, GenBank accession no. AF080594). In summary, a number of VEGF mRNA isoforms are expressed in the rat and human penis, with the splice variant encoding a 164-amino acid protein present in greatest abundance. This study is a prelude to attempts to genetically manipulate VEGF expression in the penis as a therapy for erectile dysfunction.
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PMID:Expression of messenger ribonucleic acid splice variants for vascular endothelial growth factor in the penis of adult rats and humans. 991 7

Tumor vascularization is accompanied by the migration of stromal cells, including endothelial cells, smooth muscle cells, and fibroblasts, into the tumor. The biological contributions of stromal cells to tumor vascularization have not been well-defined, partly due to the difficulty of culturing stromal cells in the presence of large numbers of fast-growing tumor cells. To address this problem, a strategy was devised to kill tumor cells but not stromal cells. Advantage was taken of the observation that diphtheria toxin (DT) kills human but not rodent cells. Human melanoma (MMAN) tumor cells were injected subcutaneously into nude mice. The tumors were excised, homogenized, and treated with 50 ng/ml DT for 24 hours. Elimination of melanoma cells by DT treatment was demonstrated by lack of detectable levels of microphthalmia, a transcription factor that is a marker for melanoma cells. The murine stromal cells were viable and found to be mostly smooth muscle cells. These cells constituted about 1.5% of the MMAN tumor. RNase protection assays using a specific murine vascular endothelial growth factor probe confirmed the murine origin of the stromal cells. This method allows rapid isolation of stromal cells and should facilitate biochemical and genetic analysis of tumor-stromal interactions.
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PMID:Isolation of mouse stromal cells associated with a human tumor using differential diphtheria toxin sensitivity. 1048 30

Expression of angiogenesis-associated genes was compared in 32 primary non-small cell lung carcinoma samples (14 adenocarcinomas, 17 squamous cell carcinomas, and 1 large cell carcinoma) and paired adjacent noncancerous lung tissues using a multiprobe RNase protection assay. Levels of Tie2, angiopoietin (Ang)-1, vascular endothelial growth factor (VEGF), and CD31 mRNAs were higher in cancers than in adjacent noncancerous tissues, in contrast to the fms-like tyrosine kinase (Flt)-1, Flt-4, Tie1, thrombin receptor, endoglin, and VEGF-C, for which no differences were evident. Overexpression did not seem to differ with histological type and pathological stage. Significant positive correlations were found between mRNA expression of Ang-1 and those of Tie2 and CD31, and that of VEGF and those of Flt-1 and CD31. These findings suggest that Ang-1 and VEGF are important angiogenic factors in human non-small cell lung carcinomas.
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PMID:Enhanced expression of Tie2, its ligand angiopoietin-1, vascular endothelial growth factor, and CD31 in human non-small cell lung carcinomas. 1049 26

Angiogenins are proteins in the pancreatic ribonuclease superfamily that utilize their ribonuclease activity to induce formation of new blood vessels. Recently we identified a new member of the angiogenin gene family, mouse angiogenin-3, by virtue of its transcriptional activation in NIH3T3 fibroblasts coincident with transformation by the chimeric leukemia oncogene, E2a-Pbx1. Here we have isolated the cDNA encoding mouse angiogenin-3 and used it to produce the protein in E. coli. We demonstrate that mouse angiogenin-3 is a ribonuclease whose activity and specificity towards tRNA and dinucleotide substrates differ from those of mouse angiogenin or of mouse angiogenin-related protein, a non-angiogenic factor. Mouse angiogenin-3 induced angiogenesis in both the chicken embryo chorioallantoic membrane assay and the rat cremaster muscle. Electron microscopy revealed that endothelial cells within vessels induced by both mouse angiogenin-3 and mouse angiogenin contain fenestrations similar to those observed in endothelial cells from neovasculature induced by vascular endothelial growth factor and basic fibroblast growth factor. Mouse angiogenin-3 also induced other molecular events typical of rapidly proliferating endothelial cells, such as increases in rough endoplasmic reticulum, polysomes, and mitochondria.
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PMID:mAngiogenin-3, a target gene of oncoprotein E2a-Pbx1, encodes a new angiogenic member of the angiogenin family. 1059 12

The expression and localization of selected growth factor systems and extracellular matrix (ECM) components that may influence oocyte maturation and fertilization within the mammalian oviduct are reported. Fibroblast growth factor (FGF) and vascular endothelial growth factor (VEGF) systems could be detected by use of RT-PCR, RNase protection assay (RPA) and immunohistochemistry in bovine follicles, bovine cumulus-oocyte complexes (COC) and bovine and marmoset oviducts. Two different subtypes of the FGF receptor (FGFR-1 and -2) were identified in distinct cell types, indicating a functional difference. A complete epidermal growth factor (EGF) system was found in the porcine, but not in the bovine, oviduct. There were additional differences between bovine and primate oviducts: FGF-1/2 and FGFR were increased in the marmoset around ovulation, in contrast to an increase in FGF-1 in the cow. Immunohistochemistry revealed accumulation and storage of FGF and VEGF on the surface of the epithelium, possibly due to their binding property on heparanglycoproteins. Other ECM components, matrix metalloproteinase 1 (MMP-1) and tissue inhibitor of metalloproteinase 1 (TIMP-1), were found to be modulated in the ovarian follicle, COC and oviduct during the cycle. An oviduct-mediated depletion of sperm surface proteins (BSP1-3) was discovered as well as a sperm-induced novel oviductal mRNA related to an anti-oxidant protein family. Associated systems of growth factors and ECM components can be suggested as paracrine or autocrine mediators during fertilization in a species-, cycle- and tissue-dependent manner.
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PMID:Growth factors and extracellular matrix proteins in interactions of cumulus-oocyte complex, spermatozoa and oviduct. 1069 68

Evenomation by arachnids of the genus Loxosceles frequently results in disfiguring necrotic skin lesions. The cellular and molecular mechanisms which contribute to lesion development are incompletely defined but appear to involve participation of several pro-inflammatory mediators. We have recently observed that Loxosceles deserta venom induces the production of chemokines in human umbilical vein endothelial cells (HUVECs) and human pulmonary epithelial cells. In the present study we observed that Loxosceles deserta venom induces the expression of vascular endothelial growth factor (VEGF) in human keratinocytes but little in smooth muscle cells and none in pulmonary epithelial cells. A potent endothelial cell-specific mitogen, VEGF induces angiogenesis and vascular permeability in vivo. RNase protection assay data indicate that VEGF mRNA concentrations in keratinocytes are significantly increased at 2 h following venom exposure. These data suggest that keratinocyte-derived VEGF may contribute to the vasodilation, edema and erythema which occur following Loxosceles evenomation.
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PMID:Loxosceles deserta spider venom induces the expression of vascular endothelial growth factor (VEGF) in keratinocytes. 1070 59

Angiopoietins are ligands for the endothelial cell tyrosine kinase receptor Tie-2. Ang-1, the major physiological activator of Tie-2, promotes blood vessel maturation and stability. Ang-2 counteracts this effect by competitively inhibiting the binding of Ang-1 to Tie-2. Using a combined RNase protection/semiquantitative reverse transcriptase-polymerase chain reaction approach, we demonstrate that hypoxia up-regulates Ang-2 mRNA levels by up to 3.3-fold in two human endothelial cell lines. In bovine microvascular endothelial (BME) cells, the flavoprotein oxidoreductase inhibitor diphenylene iodonium (DPI) and the related compound iodonium diphenyl mimic induction of Ang-2 but not vascular endothelial growth factor (VEGF) by hypoxia; in combination with hypoxia, DPI further increases Ang-2 expression but has no effect on the induction of VEGF by hypoxia. Neither Ang-2 or VEGF was increased by cyanide or rotenone, suggesting that failure in mitochondrial electron transport is not involved in the oxygen-sensing system that controls their expression. In ischemic rat dorsal skin flaps or in the brain of rats maintained for 12 hours under conditions of hypoxia, Ang-2 mRNA was up-regulated 7.5- or 17.6- fold, respectively. VEGF was concomitantly increased, whereas expression of Ang-1, Tie-2, and the related receptor Tie-1 was unaltered. In situ hybridization localized Ang-2 mRNA to endothelial cells in hypoxic skin. These findings 1) show that up-regulation of Ang-2 by hypoxia occurs widely in endothelial cells in vitro and in vivo; 2) suggest that induction of Ang-2, but not VEGF, by hypoxia in BME cells is controlled by a flavoprotein oxidoreductase that is sensitive to iodonium compounds; and 3) point to Ang-2 and VEGF as independently regulated and selective effectors of hypoxia-induced vascular sprouting.
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PMID:Hypoxia-inducible angiopoietin-2 expression is mimicked by iodonium compounds and occurs in the rat brain and skin in response to systemic hypoxia and tissue ischemia. 1085 29

It is widely assumed that, after ovulation, the human endometrium undergoes specific changes and becomes receptive to the implantation of embryo during the mid-secretory phase. When implantation does not take place, further changes occur which eventually result in the shedding of human endometrium. The present study was carried out to examine whether there are changes in the cytokine gene expression in human endometrium which are correlated with endometrial function in various phases of the menstrual cycle. The RNase protection assay was performed on carefully dated endometria from normal subjects to characterize the expression of cytokines which potentially contribute to endometrial function. These included: tumour necrosis factor (TNF), interleukin (IL)-1beta, IL-6, IL-8, leukaemia inhibitory factor (LIF), transforming growth factor beta1 (TGF-beta1), macrophage colony stimulating factor (MCSF or colony stimulating factor-1), and vascular endothelial growth factor (VEGF) mRNAs. A low level of expression of these cytokine mRNAs was found during the proliferative and early secretory phase. Expression of cytokine mRNA increased during the mid-secretory phase and rose to a peak in the late secretory phase. The level of cytokine mRNA expression during gestation was most akin to that observed during the mid-secretory phase. Individuals with habitual abortion presented with an abnormal expression of IL-1beta and IL-6 mRNA in endometrium, during the mid-secretory phase. Taken together, these findings are consistent with a progressive rise in the expression of cytokines in human endometrium during the secretory phase in natural cycles. Furthermore, the findings show that habitual abortion is associated with the abnormal expression of IL-1beta and IL-6 in the mid-secretory phase.
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PMID:Regulated expression of cytokines in human endometrium throughout the menstrual cycle: dysregulation in habitual abortion. 1087 50

The presence of vascular endothelial growth factor (VEGF) in the ovary has been reported in a number of species. The objective of the present study was to demonstrate the expression of VEGF, VEGF receptor (R)-1, and VEGFR-2 in detail by different methodological approaches in bovine corpora lutea (CL) obtained from different stages of the estrous cycle and during pregnancy. VEGF and VEGF receptor transcripts were analyzed by reverse transcription-polymerase chain reaction (RT-PCR) and ribonuclease protection assay. All components of the VEGF system were found in the bovine CL during the estrous cycle and pregnancy. Analysis of VEGF transcript by RT-PCR shows that CL tissues expressed predominantly the smallest isoforms (VEGF(121) and VEGF(165)). The highest mRNA expression for VEGF and VEGFR-2 mRNA was detected during the early luteal phase, followed by a significant decrease of expression during the mid and late luteal phase and a further decrease of VEGF mRNA after regression. During pregnancy, high levels of expression were always present. In contrast, no significant change in VEGFR-1 mRNA expression during the estrous cycle and pregnancy was found. The VEGF protein concentration in CL tissue was significantly higher (20.9-23.4 ng/g wet weight) during the early luteal phase (Days 1-7), followed by a decrease at the late luteal phase (14.3-18.7 ng/g wet weight) and, especially, after CL regression (2.8 ng/g wet weight). However, relatively high levels were found during pregnancy (10.1 ng/g wet weight). As achieved by immunohistochemistry, VEGF protein was localized predominantly in luteal cells. High VEGF protein and transcript concentrations and increased VEGFR-2 expression during the early luteal phase coincided with luteal vascularization. These results suggest an important role of VEGF in angiogenesis of the newly formed CL. The high VEGF mRNA expression and protein levels during matured vasculature in the mid-stage CL and pregnancy also suggest also a survival function for endothelial cells.
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PMID:Expression and tissue concentration of vascular endothelial growth factor, its receptors, and localization in the bovine corpus luteum during estrous cycle and pregnancy. 1099 33

This study addresses a mechanism by which lymphocytes may promote vascular endothelial growth factor (VEGF) expression and angiogenesis in immune inflammation. Resting human umbilical endothelial cells (HUVECs) were found to express low levels of VEGF messenger RNA (mRNA) by reverse transcription polymerase chain reaction and ribonuclease protection assay with little or no change in expression following activation by cytokines, including tumor necrosis factor-alpha, interleukin (IL)-1, interferon gamma, or IL-4. In contrast, treatment of HUVECs and monocytes with soluble CD40 ligand (sCD40L) resulted in a marked dose-dependent induction of VEGF mRNA (approximately 4-fold), which peaked between 1 and 5 hours post-stimulation. Transient transfection of HUVECs was performed with a luciferase reporter construct under the control of the human VEGF promoter. Treatment of transfected HUVECs with sCD40L was found to enhance luciferase activity (approximately 4-fold) compared with controls, similar to the relative fold induction in mRNA expression in parallel cultures. Thus, CD40-dependent VEGF expression was a result of transcriptional control mechanisms. Treatment of HUVECs with sCD40L was also found to function in vitro to promote growth and proliferation in a VEGF-dependent manner, and CD40-dependent HUVEC growth was comparable to that found following treatment with recombinant human VEGF. Furthermore, subcutaneous injection of sCD40L in severe combined immunodeficient and nude mice induced VEGF expression and marked angiogenesis in vivo. Taken together, these findings are consistent with a function for CD40L-CD40 interactions in VEGF-induced angiogenesis and define a mechanistic link between the immune response and angiogenesis. (Blood. 2000;96:3801-3808)
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PMID:Ligation of CD40 induces the expression of vascular endothelial growth factor by endothelial cells and monocytes and promotes angiogenesis in vivo. 1109 63


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