Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.27.1 (RNase)
 16,360 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Alveolar macrophages have been shown to bind glycoproteins and synthetic glycoconjugates (neoglycorpoteins) that have mannose, N-acetylglucosamine, or glucose in the exposed, nonreducing position. Galactose-terminal glycoproteins are not bound. Binding of radiolabeled ligands to cells is nearly completely impaired by the presence of an excess of yeast mannan. Binding is temperature sensitive and proceeds optimally at pH 7.0. Prior treatment of the cells with trypsin severely decreases their capacity to bind ligands. An inhibition assay has been developed, using radioiodinated glucose-albumin conjugate, agalacto-orosomucoid, beta-glucuronidase, and RNase B as ligands. Various glycoproteins have been shown to be effective inhibitors of ligand binding including horseradish peroxidase, agalacto-orosomucoid, beta-glucuronidase, ovalbumin, agalacto-fetuin, and RNase B. RNase A and asialo-fetuin are ineffective as antagonists. The results suggest the presence of a cell surface receptor on alveolar macrophages that binds glycoproteins having terminal sugars with the mannose or glucose configuration.
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PMID:Evidence for receptor-mediated binding of glycoproteins, glycoconjugates, and lysosomal glycosidases by alveolar macrophages. 27 29

The mitogenic activity of epidermal growth factor (EGF) is mediated by a cell surface receptor (EGF-R) which has been identified in human prostate tissues. Because of conflicting reports on the relative levels of EGF-R in prostate tumors as measured by binding of radiolabelled EGF, we have examined EGF-R expression at the level of the specific messenger RNA using a sensitive RNase protection assay. Expression of the mRNA for EGF-R was higher in carcinoma (CaP, N = 38) than in benign prostatic hyperplasia (BPH, N = 35) samples (p less than 0.01). The highest levels of EGF-R mRNA were found in the human prostatic carcinoma cell lines, PC-3 and DU145. Among the CaP samples, there was an association of higher EGF-R mRNA levels with higher tumor extent and dedifferentiation. Since EGF has also been found in prostatic tissues, the enhanced expression of the EGF-R gene may play a role in the growth of prostate tumors, possibly by an autocrine pathway.
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PMID:Epidermal growth factor receptor mRNA levels in human prostatic tumors and cell lines. 169 88

The low density lipoprotein receptor-related protein (LRP) is a multifunctional cell surface receptor, expressed in liver, that binds with high affinity and endocytoses several structurally and functionally distinct ligands, including apolipoprotein E-activated beta-migrating very low density lipoprotein, tissue-type plasminogen activator, and alpha 2-macroglobulin. Here using in situ hybridization and quantitative RNase protection assays, we show that LRP is also expressed throughout the brain. LRP message is particularly high in the cerebellum, cortex, hippocampus, and brain stem. In addition, we demonstrate that a 39-kDa protein which copurifies with LRP and regulates the binding of other ligands to LRP is also expressed throughout the brain. Interestingly, expression of the 39-kDa message is approximately 100-fold of that found in liver, suggesting that the activity of LRP is more tightly regulated in brain tissue than in liver. Using primary cultures of isolated postnatal cortical neurons, [35S]methionine biosynthetic labeling and immunoprecipitation, we also demonstrate the de novo biosynthesis of LRP, the 39-kDa protein, as well as tissue-type plasminogen activator. Finally, using radioligand binding as well as fluorescent ligand binding and uptake studies, we show that LRP is functional in cortical neurons. These results taken together thus demonstrate expression of functional LRP in neuronal cells and suggest a potential role for LRP in brain protein and lipoprotein metabolism, development, and regeneration.
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PMID:Expression and function of the low density lipoprotein receptor-related protein (LRP) in mammalian central neurons. 751 35

Scatter factor/hepatocyte growth factor (SF/HGF) has potent motogenic, mitogenic, and morphogenetic activities on epithelial cells in vitro. The cell surface receptor for this factor was recently identified: it is the product of the c-met protooncogene, a receptor-type tyrosine kinase. We report here the novel and distinct expression patterns of SF/HGF and its receptor during mouse development, which was determined by a combination of in situ hybridization and RNase protection experiments. Predominantly, we detect transcripts of c-met in epithelial cells of various developing organs, whereas the ligand is expressed in distinct mesenchymal cells in close vicinity. In addition, transient SF/HGF and c-met expression is found at certain sites of muscle formation; transient expression of the c-met gene is also detected in developing motoneurons. SF/HGF and the c-met receptor might thus play multiple developmental roles, most notably, mediate a signal given by mesenchyme and received by epithelial. Mesenchymal signals are known to govern differentiation and morphogenesis of many epithelia, but the molecular nature of the signals has remained poorly understood. Therefore, the known biological activities of SF/HGF in vitro and the embryonal expression pattern reported here indicate that this mesenchymal factor can transmit morphogenetic signals in epithelial development and suggest a molecular mechanism for mesenchymal epithelial interactions.
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PMID:Scatter factor/hepatocyte growth factor and its receptor, the c-met tyrosine kinase, can mediate a signal exchange between mesenchyme and epithelia during mouse development. 840

The cell surface receptor Fas (FasR, Apo-1, CD95) and its ligand (FasL) are mediators of apoptosis that have been shown to be implicated in the peripheral deletion of autoimmune cells, activation-induced T cell death, and one of the two major cytolytic pathways mediated by CD8+ cytolytic T cells. To gain further understanding of the Fas system., we have analyzed Fas and FasL expression during mouse development and in adult tissues. In developing mouse embryos, from 16.5 d onwards, Fas mRNA is detectable in distinct cell types of the developing sinus, thymus, lung, and liver, whereas FasL expression is restricted to submaxillary gland epithelial cells and the developing nervous system. Significant Fas and FasL expression were observed in several nonlymphoid cell types during embryogenesis, and generally Fas and FasL expression were not localized to characteristic sites of programmed cell death. In the adult mouse, RNase protection analysis revealed very wide expression of both Fas and FasL. Several tissues, including the thymus, lung, spleen, small intestine, large intestine, seminal vesicle, prostate, and uterus, clearly coexpress the two genes. Most tissues constitutively coexpressing Fas and FasL in the adult mouse are characterized by apoptotic cell turnover, and many of those expressing FasL are known to be immune privileged. It may be, therefore, that the Fas system is implicated in both the regulation of physiological cell turnover and the protection of particular tissues against potential lymphocyte-mediated damage.
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PMID:Fas and Fas ligand in embryos and adult mice: ligand expression in several immune-privileged tissues and coexpression in adult tissues characterized by apoptotic cell turnover. 860 66

The cell surface receptor Fas (FasR, Apo-1, CD95) and its ligand (FasL) are mediators of apoptosis which have been shown to be implicated in peripheral deletion of autoimmune cells, activation-induced T cell death, and one of the two major cytolytic pathways mediated by CD8+ cytolytic T cells. Analysis of FasL expression during mouse embryogenesis and in adult tissues reveals that FasL, although initially thought to be restricted to lymphoid cells, is constitutively expressed in a wide array of non lymphoid tissues. FasL mRNA is detectable in mouse embryos from 16.5-d onwards in epithelial cells of the submaxillary gland, and neurons of the developing nervous system. In general, FasL mRNA was not detectable in characteristic sites of embryonic programmed cell death. In the adult mouse, by RNase protection analysis, FasL mRNA is detectable in all 20 tissues tested except for the heart and pancreas. Similar analysis performed simultaneously for Fas indicates that several tissues, including the thymus, lung, spleen, small intestine, liver, seminal vesicle, prostate and uterus co-express the two genes. Most tissues constitutively co-expressing Fas and FasL in the adult mouse are characterized by apoptotic cell turnover, and many of those expressing FasL are known to be immune-privileged. The pattern of FasL expression in mice suggests that FasL may be implicated in the regulation of physiological cell turnover, and the protection of tissues against potential lymphocyte mediated damage.
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PMID:Constitutive Fas ligand expression in several non-lymphoid mouse tissues: implications for immune-protection and cell turnover. 895 Apr 73

Tissue factor (TF) is the primary cellular initiator of the coagulation protease cascade and serves as a cell surface receptor and a specific cofactor for plasma factors VII/VIIa. Because there is evidence that TF is regulated by a P-selectin dependent gene, we examined TF mRNA expression in the lungs during murine traumatic shock in the presence and absence of recombinant soluble P-selectin glycoprotein ligand-1 (rsPSGL.Ig) by using ribonuclease protection assays. Moreover, we studied the level of TF mRNA expression in mice with their P-selectin gene deleted (P-selectin -/-). Our data show that TF mRNA was significantly increased (+143%; P < 0.001) in the lungs 2 h after trauma compared with control rats subjected to sham trauma, which exhibited reduced TF mRNA expression (-34%; P < 0.001) after systemic administration of rsPSGL.Ig. The expression of TF mRNA was also significantly decreased (-29%; P < 0.05) in the lungs of P-selectin -/- mice compared with wild-type control C57B16 mice. The present results provide evidence for a P-selectin-dependent mechanism that enhances TF gene expression in traumatic shock. The major support for this mechanism is that either blockade of P-selectin by rsPSGL.Ig or deletion of the P-selectin gene leads to significant decreases in TF mRNA expression in the lung. These results are consistent with the concept that TF interacting with P-selectin may play a significant role in the pathophysiology of trauma.
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PMID:Pulmonary tissue factor mRNA expression during murine traumatic shock: effect of P-selectin blockade. 1130 34

We report a new tumor-directed immunoRNase, a chimeric protein made up of an antibody fragment (single-chain Fv fragment) directed to ErbB2, a cell surface receptor, and a non-toxic, human ribonuclease, which upon cell internalization becomes cytotoxic. The immunoRNase is active as a ribonuclease, specifically binds and selectively kills ErbB2-positive cells. ErbB2 is one of the most specific tumor-associated antigens identified so far, overexpressed on tumor cells of different origin. Its choice as target antigen and that of a non-toxic, human RNase as the killer moiety makes this immunoRNase a new, potentially attractive anticancer agent.
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PMID:A new RNase-based immunoconjugate selectively cytotoxic for ErbB2-overexpressing cells. 1195 34

Antisense-mediated degradation of target mRNA is achieved by the enzymatic action of nuclease RNase H. The enzyme recognizes hybrid RNA-DNA duplexes and hydrolyzes the RNA strand. Here, we compared six different phosphorothioate oligonucleotides for their ability to induce target-specific mRNA degradation in cultured mouse AML12 cells. We targeted transcripts of the cell surface receptor Fas and analyzed the levels of mRNA by Northern blotting and ribonuclease protection assay (RPA). Four of the tested antisense oligonucleotides reduced the mRNA levels significantly. Cultures treated with one of the antisense molecules resulted in a shifted band on Northern blots. This band of lower molecular weight was not detected after 6 hours of transfection but appeared at 24 hours. By RPA, the product was shown to be a 3'-cleavage fragment of the full-length Fas mRNA. The RPA also mapped the stable fragment to start within the antisense complementary sequence.
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PMID:Antisense-induced Fas mRNA degradation produces site-specific stable 3'-mRNA fragment by exonuclease cleavage at the complementary sequence. 1562 17

2-Methoxyestradiol is a physiologic metabolite of 17beta-estradiol. This orally active compound can inhibit tumor growth or metastasis in tumor models without inducing any clinical sign of toxicity. Our previous studies indicated that 2-methoxyestradiol-mediated apoptosis involves the disappearance of intact 21-kDa Bid protein, cytochrome c release, and predominant procaspase-3 cleavage. Here, using MIA PaCa-2 cells as a model, we investigated whether this estrogen metabolite induces apoptosis by converging two major pathways: the death receptor-mediated extrinsic and the mitochondrial intrinsic pathway. Exogenous expression of dominant-negative caspase-8 or dominant-negative FADD reverts the effect of 2-methoxyestradiol-mediated cell death. In parallel with this observation, Z-IETD-FMK, a cell permeable irreversible inhibitor of caspase-8, can render significant protection against 2-methoxyestradiol-induced apoptosis. RNase protection assay and cell surface receptor analysis by flow cytometry show the up-regulation of members of death receptor family in 2-methoxyestradiol-exposed pancreatic cancer cells. Our mechanistic studies also implicate that oxidative stress precedes 2-methoxyestradiol-mediated c-Jun NH2-terminal kinase activation, leading to elevated Fas level. Because 2-methoxyestradiol is able to trigger death receptor signaling, we were interested in examining the effects of 2-methoxyestradiol and Fas ligand (FasL)/tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) together on pancreatic cancer cell death. Interestingly, the endogenous angiogenesis inhibitor 2-methoxyestradiol augments FasL/TRAIL-induced apoptosis in these cells. Moreover, the combination of 2-methoxyestradiol and TRAIL reduces the tumor burden in vivo in MIA PaCa-2 tumor xenograft model by caspase-3 activation.
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PMID:Crosstalk between extrinsic and intrinsic cell death pathways in pancreatic cancer: synergistic action of estrogen metabolite and ligands of death receptor family. 1661 56


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