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:3.1.27.1 (RNase)
16,360 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The tyrosine kinase receptor c-kit and its ligand KL are required for postnatal development of germ cells, in addition to their role in primordial germ cells. To clarify their function, a detailed examination of the pattern of expression of KL in postnatal gonads was undertaken. In ovaries, the expression of KL as seen by RNA blot analysis and by RNase protection assays is relatively high at birth (P0), low from P5 to P8, and high from P12 onward. KL expression is relatively high in testes of all ages. The forms of KL RNA present in the testes suggest that from P5 onward the membrane-bound form of KL predominates, while in the ovary significant amounts of both forms are present. As observed by in situ hybridization and immunohistochemistry, in the newborn ovary KL is highly expressed in central cords whose cells contribute to the formation of central growing follicles. Expression is low in follicle cells of small growing follicles and increases to high levels in three-layered follicles during late oocyte growth. Large amounts of the ligand are found within growing oocytes. After oocyte growth ceases, expression continues only in the outer layers of multilayered follicles. In the testis, from P0 through P9, KL expression is distinct in Sertoli cells, but not in germ cells. Thereafter, the intensity of KL expression declines as the number of spermatogenic cells increases within the tubules. KL in Sertoli cells appears to be concentrated basally at the stage of the cycle of the seminiferous epithelium when it is known to interact with differentiating type A spermatogonia. These data are consistent with a role for KL in oocyte growth and in facilitating proliferation and/or differentiation of type A spermatogonia.
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PMID:The expression pattern of the c-kit ligand in gonads of mice supports a role for the c-kit receptor in oocyte growth and in proliferation of spermatogonia. 768 86

Steel factor (SF), the ligand for c-kit, is an essential regulator of normal hematopoiesis, melanogenesis, gametogenesis, and mast-cell growth and development. Hematopoietic stromal cells are important sources of SF, because inactivation of SF in mice results in defects in the support function of hematopoietic stromal cells. To identify specific cells that produce, and factors that govern the expression of the different isoforms of SF in human hematopoiesis, we quantified levels of SF mRNA and membrane-bound protein in human stromal cells before and after exposure to recombinant human interleukin (IL)-1 alpha, a cytokine known to induce the expression of a variety of hematopoietic growth factors. In addition, because stromal cells in longterm bone marrow cultures (LTBMC) are supportive of hematopoietic progenitor cell survival in vitro, while umbilical vein endothelial cells (EC) and diploid fibroblasts (DF) are not, we also sought to test the hypothesis that SF gene expression would differ in cells from LTBMC when compared with EC or DF. Using reverse-transcription polymerase chain reaction amplification (RT-PCR), ribonuclease protection assays (RPA), and Northern blot analysis, SF was found to be constitutively transcribed in EC, DF, and LTBMC. IL-1 alpha neither induced accumulation of SF mRNA nor altered the ratio of exon 6+ to exon 6- transcripts in these stromal cells. By Northern blot analysis, the predominant SF mRNA species was shown to be 5.6 kb; a minor population of 3.6 kb was also found. Low levels of membrane-bound SF protein were found to be constitutively expressed by all three types of stromal cells, and were not regulated by IL-1 alpha. We conclude that the unique capacity of LTBMC to support in vitro hematopoiesis, when compared with EC or DF, cannot be explained on the basis of qualitative or quantitative differences in SF gene expression in these cells.
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PMID:Constitutive expression of steel factor gene by human stromal cells. 768 92

Angiotensin I-converting enzyme (ACE) is known to be present at the surface of endothelial cells and also in the adventitia in large vessels. The presence of ACE in the vascular smooth muscle remains controversial. We microdissected segments of adventitia and media with or without endothelium from a region devoid of collateral arteries. The membrane-bound ACE activity in the media averaged 41% (pmol [glycine-1-14C]hippuryl-L-histidyl-L-leucine hydrolyzed.g tissue-1.min-1) of the values found in the whole aorta, whereas the adventitia contained only 6%. Immunoreactive ACE in media was characterized by Western blotting. ACE mRNAs were detected and characterized after polymerase chain amplification in isolated media. Angiotensin I and angiotensin II were equally able to contract medial rings, and the response to angiotensin I was blocked by enalaprilat. In aortas of two-kidney, one-clip hypertensive rats, there was an increase in ACE mRNA estimated by ribonuclease protection assay (P = 0.02) and in ACE activity at 15 days and 1 and 3 mo after clipping. This corresponded to a 1.5- to 2-fold increase in the ACE activity of both the media and the adventitia compared with sham-operated rats (P < or = 0.02). Thus ACE gene expression occurs in smooth muscle of rat aorta, which contains roughly the same amount of enzyme as the endothelium and readily converts angiotensin I to angiotensin II. ACE in the medial layer and the adventitia is upregulated in renovascular hypertension.
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PMID:ACE in three tunicae of rat aorta: expression in smooth muscle and effect of renovascular hypertension. 797 8

Splenic B cells from BALB/c mice bearing mammary adenocarcinomas are capable of performing Ab-dependent cellular cytotoxicity. Effector-target conjugation after 18 h results in minimal cytoplasmic damage, whereas extensive nuclear disintegration is observed. To determine whether splenic B cells from tumor-bearing mice can effect direct cytotoxicity against tumor cells, L929 and WEHI 164 cells were used as targets. B lymphocytes from tumor-bearing mice, but not from normal animals, were capable of lysing these two types of tumor cells. However, only a low level of cytotoxicity could be detected when the nontumorigenic 3T3 cells were used as targets. To elucidate the mechanism of cytotoxicity of these killer B cells, RNase protection assays were performed using perforin, granzyme A, TNF-alpha, and lymphotoxin probes. No perforin, granzyme A, or lymphotoxin RNA could be detected in purified preparations of B cells from normal and tumor-bearing mice. B cells from normal mice did not have TNF-alpha RNA. In contrast, B cells from tumor bearers expressed TNF-alpha RNA. TNF-alpha could be detected in supernatants from both unstimulated and stimulated tumor bearers' splenic B cells, as measured by ELISA, and its lytic activity was neutralized by anti-TNF-alpha Ab. Western blots revealed the presence of TNF-alpha on the surface of the killer B cells. Paraformaldehyde-fixed B cells from tumor-bearing mice but not from normal animals were able to lyse TNF-alpha-sensitive tumor targets. This cytotoxicity was neutralized by anti-TNF-alpha Ab. These results suggest that TNF-alpha in soluble and membrane-bound forms may be involved in the mechanism of cytotoxicity exerted by B cells from tumor-bearing mice.
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PMID:Soluble and membrane-bound TNF-alpha are involved in the cytotoxic activity of B cells from tumor-bearing mice against tumor targets. 814 19

Systemic interleukin-1 (IL-1) activates the hypothalamo-pituitary-adrenal (HPA) axis, an effect exerted through increased synthesis and secretion of corticotropin-releasing factor (CRF) by parvicellular neurosecretory neurons. The site(s) and mechanism(s) through which circulating IL-1 may access central systems governing HPA axis output remain obscure. To identify potential cellular targets for blood-borne IL-1, we analyzed the distribution of mRNA encoding the rat type 1 IL-1 receptor (IL-1R1) in rat brain. Regional ribonuclease protection assays detected a single protected fragment corresponding to the membrane-bound form of the IL-1R1 mRNA in all areas analyzed. In situ hybridization revealed labeling predominantly over barrier-related cells, including the leptomeninges, non-tanycytic portions of the ependyma, the choroid plexus, and vascular endothelium. Low to moderate levels of the IL-1R1 mRNA were detected in just a few neuronal cell groups, including the basolateral nucleus of the amygdala, the arcuate nucleus of the hypothalamus, the trigeminal and hypoglossal motor nuclei, and the area postrema. No specific labeling for IL-1R1 mRNA was detected over neurons that respond to intravenous IL-1 beta by induction of transcription factor Fos, including hypophysiotropic CRF cells and brainstem catecholamine neurons. Injection of IL-1 beta did, however, provoke induction of mRNA encoding the immediate-early gene, NGFI-B, but not c-fos, in two major loci of IL-1R1 expression, vascular endothelial cells, and the area postrema. Intravenous injection of IL-1 beta acutely down-regulated IL-1R1 mRNA in perivascular cells, but not in neuronal cell groups. These results suggest the parenchymal sites of IL-1R1 expression in rat to be distinct from those reported previously in mouse. The common expression in both species of an IL-1R in non-neuronal elements highlights the possibility that IL-1-mediated activation of CRF neurons may result from cytokine-receptor interaction at vascular, and/or other barrier-related, sites to trigger release of secondary signalling molecules in a position to interact with components of HPA control circuitry.
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PMID:Type 1 interleukin-1 receptor in the rat brain: distribution, regulation, and relationship to sites of IL-1-induced cellular activation. 857 22

The occurrence of multidrug resistance (MDR) is one of the main obstacles in the successful chemotherapeutic treatment of cancer. MDR cell lines are resistant to the so-called naturally occurring anti-cancer drugs, such as anthracyclines, Vinca alkaloids and epipodophyllotoxins, but are not cross-resistant to alkylating agents, antimetabolites and cisplatin. So far, three separate forms of MDR have been characterized in more detail: classical MDR, non-Pgp MDR and atypical MDR. Although all three MDR phenotypes have much in common with respect to cross-resistance patterns, the underlying mechanisms certainly differ. Atypical MDR is associated with quantitative and qualitative alterations in topoisomerase II alpha, a nuclear enzyme that actively participates in the lethal action of cytotoxic drugs. Atypical MDR cells do not overexpress P-glycoprotein, and are unaltered in their ability to accumulate drugs. In this review we will focus on classical and non-Pgp MDR. The molecular mechanism of classical and non-Pgp MDR is transcriptional activation of membrane-bound transport proteins. These transport proteins belong to the ATP-binding cassette (ABC) superfamily of transport systems. The classical MDR phenotype is characterized by a reduced ability to accumulate drugs, due to activity of an energy-dependent uni-directional, membrane-bound, drug-efflux pump with broad substrate specificity. The classical MDR drug pump is composed of a transmembrane glycoprotein (P-glyco-protein-Pgp) with a molecular weight of 170 kD, and is, in man, encoded by the so-called multidrug resistance (MDR1) gene. Typically, non-Pgp MDR has no P-gly-coprotein expression, yet has about the same cross-resistance pattern as classical MDR. This non-Pgp MDR phenotype is caused by overexpression of the multidrug resistance-associated protein (MRP) gene, which encodes a 190 kD membrane-bound glycoprotein (MRP). MRP probably works by direct extrusion of cytotoxic drugs from the cell and/or by mediating sequestration of the drugs into intracellular compartments, both leading to a reduction in effective intracellular drug concentrations. For the classical MDR phenotype, evidence is accumulating that it plays a role indeed, in clinical drug resistance, especially in some hematological malignancies (acute myeloid leukemia, multiple myeloma and non-Hodgkin's lymphoma) and solid tumors (soft tissue sarcomas and neuroblastoma). The association of MRP with clinical drug resistance has not been elaborated, yet, and studies on MRP expression in human cancer have just begun. We found that overexpression of MRP, as determined by RNase protection assay as well as by immunohistochemistry, occurs in several human cancers, among which are cancer of the lung, esophagus, breast and ovary, and leukemias. Further studies are indicated to establish whether elevated MRP expression at diagnosis is an unfavorable prognostic factor for clinical outcome of chemotherapy.
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PMID:Molecular mechanisms of multidrug resistance in cancer chemotherapy. 888 Aug 78

We have developed a nonisotopic RNase protection assay using RNA probes that are dual-labeled with biotin and fluorescein for detection. This system utilizes capture of the protected RNA probe hybrids to streptavidin-coated membranes attached to plastic dipsticks, complexing of anti-fluorescein-urease conjugate with the labeled RNA probe, and quantitative detection of the membrane-bound complex by a potentiometric silicon sensor. The dual-label RNase protection (RP) assay was capable of measuring beta-actin mRNA in cellular RNA samples at the 27- to 45-amol level (10-17 pg) with high precision (%CV < 7). We have used this method to quantitate the levels of erbB-2 mRNA in the human tumor cell lines SKBR-3, SKOV-3, and MCF-7. The levels of erbB-2 mRNA in these cells were 105, 190, and 0.9 amol per microgram of cellular RNA, respectively. The dual-label RP method should be useful for measuring the mRNA expression for other erbB-2 homologs such as erbB-3 and erbB-4 in tumor cells and tissues and can be a generally useful mRNA quantitative method for laboratories wishing to minimize radioisotope use.
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PMID:Nonisotopic quantitation of mRNA using a novel RNase protection assay: measurement of erbB-2 mRNA in tumor cell lines. 893 64

Nuclear-encoded cytoplasmic tRNAs are imported into the mitochondria of kinetoplastid protozoa by an unknown mechanism. In a Leishmania in organello system, ATP-dependent import of a cloned, unspliced tRNATyr(GUA) transcript was demonstrated by protection from ribonuclease, whereas import of a tRNAGln(CUG) transcript was much less efficient. Specific binding of tRNATyr to two mitochondrial surface proteins of 15 and 22 kilodaltons was observed. Tubulin antisense-binding protein (TAB), the 15-kilodaton species, was purified to apparent homogeneity by RNA affinity chromatography. TAB forms stable complexes with the D stem-loop region of tRNATyr. Immunocytochemical and cell fractionation experiments, combined with limited proteolysis, suggested the association of TAB with the outer mitochondrial membrane. Importantly, anti-TAB antibody specifically inhibited binding as well as import of tRNATyr and of a synthetic structural homolog. These results support the role of TAB as a membrane-bound receptor or carrier for RNA import into Leishmania mitochondria.
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PMID:Role of an RNA-binding protein in import of tRNA into Leishmania mitochondria. 926 Nov 54

This paper deals with the induction of the SOS-functions of a bacterial cell by the exogenous ribonuclease of Bacillus intermedius. Two test systems were employed, which made it possible to quantitatively estimate SOS-response induction activity in gram-positive and gram-negative bacteria. It was established that the catalytically active enzyme elicits the SOS-response in the cells of Escherichia coli PQ 37 and causes prophage induction in the lysogenic strain Bacillus subtilis 168 phi 105 WT (a phenomenon related to the SOS-response). An enzyme with a His101Glu-substituted active center, exhibiting residual catalytic activity, failed to induce the SOS-response in an SOS-chromotest with E. coli PQ 37, indicating dependence of the SOS-inducing effect of the enzyme on its catalytic activity. It is suggested that the effect of active ribonuclease on membrane-bound and cytoplasmic RNA causes a change in the nucleotide pool and, as a consequence, elicits the SOS-response of the cell.
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PMID:[Induction of the SOS-response with Bacillus intermedius RNAase]. 937 68

Our previous studies suggested that enhanced fibronectin mRNA translation in ductus arteriosus compared with aortic smooth muscle cells is related to increased expression of light chain 3 (LC3) of microtubule-associated protein 1, which binds an AU-rich element in the 3' untranslated region of fibronectin mRNA. We therefore hypothesized that microtubules are involved in LC3-mediated fibronectin mRNA translational regulation. In this study we show that disruption of microtubules by colchicine inhibits fibronectin mRNA translation in cultured ductus arteriosus smooth muscle cells. We proposed that the mechanism might be related to decreased docking of fibronectin mRNA on the translational machinery, ie, membrane-bound polysomes on rough endoplasmic reticulum, and confirmed this by Northern blot analysis. To investigate the mechanism further, we carried out polysome analysis using sucrose gradient centrifugation and fractionation and studied the polysomal distribution of fibronectin mRNA and LC3 protein in the sucrose gradient by using RNase protection assay and Western immunoblotting, respectively. Colchicine treatment shifts fibronectin mRNA from the fractions containing membrane-bound polysomes to the fractions carrying free polysomes and concomitantly decreases the amount of LC3 protein in the fractions containing membrane-bound polysomes. Furthermore, an EDTA-release experiment demonstrates that LC3 protein associates with the 60S ribosomal subunit. Our data support the concept that microtubules may function with LC3 to facilitate sorting of fibronectin mRNA onto rough endoplasmic reticulum and translation.
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PMID:Microtubule involvement in translational regulation of fibronectin expression by light chain 3 of microtubule-associated protein 1 in vascular smooth muscle cells. 973 70


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