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)

CD34 is a cell surface antigen of unknown function expressed in humans in hematopoietic stem cells, vascular endothelium, and blasts from 30% of patients with acute myeloid and lymphocytic leukemia. To begin to investigate the cis-acting elements required for this tissue-specific expression, the human CD34 locus was isolated and its genomic structure and transcriptional start site were characterized. The human CD34 gene spans 26 kb and has 8 exons, a structure quite similar to that of the murine gene. The start site of CD34 transcription was determined to be 258 bp upstream of the translational start site using RNase protection. These experiments also indicated that the 5' untranslated region has extensive secondary structure. In addition, fluorescence in situ hybridization was used to map the CD34 locus to band 1q32.
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PMID:Structure of the gene encoding CD34, a human hematopoietic stem cell antigen. 137 51

Leukocyte adhesion to vascular endothelium is an early step in inflammatory damage to tissues. To investigate the expression of endothelial adhesion molecules in the inflammatory response associated with cardiopulmonary bypass, we measured messenger ribonucleic acid (mRNA) encoding the adhesion molecules E-selectin and intercellular adhesion molecule-1 in intraoperative samples of cardiac tissue and skeletal muscle from infants undergoing cardiopulmonary bypass. Atrial tissue samples were obtained before and after bypass from 11 children and paired samples of rectus abdominis muscle from 15. mRNA was analyzed by ribonuclease protection with the use of nonmuscle actin as an internal control. Atrial E-selectin mRNA levels increased from before to after bypass (median increase 3.5-fold, p = 0.0002) in each of nine patients tested, and atrial intercellular adhesion molecule-1 mRNA increased in seven of nine patients (median, 2.1-fold, p = 0.025). In skeletal muscle, E-selectin mRNA increased in 11 of 12 patients (median 4.3-fold, p = 0.0018), and intercellular adhesion molecule-1 mRNA levels increased in 13 of 13 patients (median 3.2-fold, p = 0.013). E-selectin and intercellular adhesion molecule-1 induction in skeletal muscle occurred with or without circulatory arrest. We conclude that adhesion molecule mRNA induction occurs in cardiac and noncardiac tissue during cardiopulmonary bypass in man.
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PMID:Induction of intercellular adhesion molecule-1 and E-selectin mRNA in heart and skeletal muscle of pediatric patients undergoing cardiopulmonary bypass. 751 75

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

Murine traumatic shock is associated with increased adherence of neutrophils to the vascular endothelium resulting in neutrophil infiltration and tissue damage. We examined the effects of trauma on the expression of the adhesion molecule P-selectin in several vital organs (i.e., heart, lungs, liver, kidneys, and small intestine) 2 h after induction of Noble-Collip drum trauma in anesthetized rats. Total RNA was extracted from these organs and P-selectin mRNA was quantified by RNase protection assays. P-selectin mRNA was significantly increased over control nontraumatized, anesthetized rats in all vital organs (P<0.05 or less), with the largest increase occurring in the lung (P<0.01). Immunohistochemical analysis showed increased expression of P-selectin protein in postcapillary venules of all vital organs after trauma. To further investigate the possible mechanisms of increased P-selectin mRNA transcription promoter activity during trauma, we quantified binding of proteins from nuclear extracts to the kappaB site (-218GGGGGTGACCC[-207]) of the P-selectin gene by electrophoretic mobility shift assay. We confirmed the results of NF-kappaB binding by demonstrating increases in p50 and p52, as well as decreases in IkappaB in cytoplasmic and nuclear extracts from the lungs of trauma rats by Western blotting. Increased activity of the transcription factor, nuclear factor kappaB (NF-kappaB), occurred in all vital organs of the trauma rats compared to sham-operated controls. Our findings suggest that severe trauma results in up-regulation of P-selectin at the transcriptional level, which is partly controlled by an NF-kappaB-responsive element in the region of the P-selectin promoter. This increased activation of NF-kappB binding may contribute to the widespread increases in P-selectin expression observed in several vital organs 2 h after trauma, which in turn may play a key role in the pathogenesis of traumatic shock.
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PMID:P-selectin is up-regulated in vital organs during murine traumatic shock. 940 46

Severe intrauterine growth restriction (IUGR) is characterized by abnormal placentation. Mouse gene knockout studies show that an absence of either hepatocyte growth factor (HGF) or its receptor, c-met, leads to intrauterine death secondary to severe IUGR with deficient placentation. In this study, immunocytochemistry localized HGF protein throughout placental villi across gestation, whereas c-met protein was localized only to the perivillous trophoblast and vascular endothelium. Within the IUGR placentae, a reduction in HGF immunostaining within the villous stroma was observed. HGF mRNA was strongly expressed in the perivascular tissue around the stem villous arteries throughout gestation, with weaker expression within the villous stroma and the terminal villi. c-met mRNA expression was limited to the perivillous trophoblast, particularly in the first trimester, with only a faint hybridization signal from the villous stroma. Placental mRNA expression was examined quantitatively using a ribonuclease protection assay: HGF and c-met mRNA expression increased from the first to the second trimester, reaching a zenith before decreasing again through the third trimester to term. HGF mRNA levels were significantly reduced in the IUGR placentae (P = 0.036), whereas c-met mRNA expression was within the normal range for gestation. These findings suggest that HGF derived from the perivascular tissue of stem villous arteries may play an important role in controlling normal villous development. Whereas reduced expression of HGF within IUGR placentae does not prove a causative link with abnormal villous development, the association lends support to this possibility.
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PMID:Ontogeny of hepatocyte growth factor (HGF) and its receptor (c-met) in human placenta: reduced HGF expression in intrauterine growth restriction. 977 45

Gamma delta T lymphocytes are thought to play a role in the pathogenesis of multiple sclerosis (MS) contributing to demyelinization and fibrosis in the central nervous system. In this study, we show that, in MS patients with active disease, the percentage of circulating V delta 2+ gamma delta T cells coexpressing NKRP1A is significantly increased compared with healthy donors. V delta 2+ and V delta 1+ T cells were sorted from MS patients and healthy volunteers and cloned. At variance with V delta 1+ clones, all V delta 2+ clones expressed NKRP1A, which was strongly up-regulated upon culture with IL-12; this effect was neutralized by specific anti-IL-12 Abs. No up-regulation of NKRP1A by IL-12 was noted on V delta 1+ clones. RNase protection assay showed that IL-12R beta 2 subunit transcript was significantly less represented in V delta 1+ than V delta 2+ clones. This finding may explain the different effect exerted by IL-12 on these clones. In transendothelial migration assays, V delta 2+ NKRP1A+ clones migrated more effectively than V delta 1+ clones, and this migratory potential was enhanced following culture with IL-12. Migration was strongly inhibited by the F(ab')2 of an anti-NKRP1A Ab, suggesting that this lectin is involved in the migration process. We also show that, in freshly isolated PBMC from MS patients, the migrated population was enriched for V delta 2+ NKRP1A+ cells. We conclude that the expression of NKRP1A on V delta 2+ cells is associated with increased ability to migrate across the vascular endothelium and that this phenomenon may be regulated by IL-12 present in the microenvironment.
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PMID:IL-12-mediated NKRP1A up-regulation and consequent enhancement of endothelial transmigration of V delta 2+ TCR gamma delta+ T lymphocytes from healthy donors and multiple sclerosis patients. 1020 68

Chemotactic cytokines (chemokines) play an important role in the recruitment of lymphocytes to tissue by regulating cellular adhesion and transendothelial migration. This study examined the expression and function of CXC (human monokine induced by gamma-interferon [HuMig], interleukin-8 [IL-8], and interferon-inducible protein-10 [IP-10]) and CC (macrophage inflammatory protein-1alpha [MIP-1alpha], MIP-1beta, regulated upon activation normal T lymphocyte expressed and secreted (RANTES), and macrophage chemoattractant protein-1 [MCP-1]) chemokines and their respective receptors on lymphocytes infiltrating human liver tumors. Chemokine and chemokine receptor expression was assessed by immunohistochemistry, flow cytometry, in situ hybridization and ribonuclease (RNAse) protection assays and function by in vitro chemotaxis of tumor-derived lymphocytes to purified chemokines and to HepG2 tumor cell culture supernatants. Tumor-derived lymphocytes showed strong chemotactic responses to both CC and CXC chemokines in vitro and expressed high levels of CXCR3 (HuMig and IP-10 receptor) and CCR5 (RANTES, MIP-1alpha, and MIP-1beta receptor). Expansion of tumor-derived lymphocytes in recombinant IL-2 increased expression of CXCR3. The corresponding chemokines were detected on vascular endothelium (HuMig, IL-8, MIP-1alpha, and MIP-1beta) and sinusoidal endothelium (HuMig, MIP-1alpha, MIP-1beta) in hepatocellular carcinoma. In vitro, HepG2 cells secreted functional chemotactic factors for tumor-derived lymphocytes that could be inhibited using anti-CCR5 or anti-CXCR3 monoclonal antibodies (MoAbs). Thus, lymphocytes infiltrating human liver tumors express receptors for and respond to both CXC and CC chemokines. The relevant chemokine ligands are expressed in hepatocellular carcinoma (HCC), particularly HuMig, which was strongly expressed by tumor endothelium, suggesting that they play a role in lymphocyte recruitment to these tumors in vivo. The ability of HepG2 cells to secrete lymphocyte chemotactic factors in vitro suggests that the tumor contributes to lymphocyte recruitment in vivo.
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PMID:Expression and function of CXC and CC chemokines in human malignant liver tumors: a role for human monokine induced by gamma-interferon in lymphocyte recruitment to hepatocellular carcinoma. 1038 45

Classic ischemic preconditioning transiently (30 to 120 minutes) protects the myocardium against subsequent lethal ischemia/reperfusion injury. After dissipation of this acute protection, a second window of protection (SWOP) appears 12 to 24 hours later; this SWOP lasts up to 3 days. Several triggers induce a SWOP, including brief repetitive cycles of coronary artery occlusion, rapid ventricular pacing, stimulation of adenosine A(1) receptors, and administration of wall fragments of Gram-negative bacteria, such as lipopolysaccharide (LPS). The aim of this study was to investigate whether lipoteichoic acid (LTA), a cell wall fragment of Gram-positive bacteria, can induce a SWOP in a rat model of left anterior descending coronary artery (LAD) occlusion (25 minutes) and reperfusion (2 hours). Thus, 166 male Wistar rats were pretreated (2 to 24 hours) with saline, LTA (1 mg/kg IP), or LPS (1 mg/kg IP) and subjected to LAD occlusion/reperfusion. Pretreatment with LTA or LPS for 16 hours led to a substantial, approximately 65%, reduction in infarct size and a reduction in the release of cardiac troponin T into the plasma. The dose of LTA used had no toxic effect (on any of the parameters studied), whereas the same dose of LPS caused a time-dependent activation of the coagulation system and liver injury. By use of RNase protection assays, it was determined that LPS caused a time-dependent induction of tumor necrosis factor-alpha, interleukin-1beta, and manganese superoxide dismutase mRNA content in the heart, whereas LTA failed to induce manganese superoxide dismutase. LPS also caused an upregulation of the expression of intercellular adhesion molecule-1 and P-selectin, whereas LTA downregulated these molecules and attenuated the accumulation of polymorphonuclear granulocytes caused by myocardial ischemia/reperfusion. This study demonstrates for the first time that pretreatment with LTA at 8 to 24 hours before myocardial ischemia significantly reduces (1) infarct size, (2) cardiac troponin T, and (3) the histological signs of tissue injury in rats subjected to LAD occlusion and reperfusion. The mechanism(s) underlying the observed cardioprotective effects of LTA warrants further investigation but is likely to be related to its ability to inhibit the interactions between the coronary vascular endothelium and polymorphonuclear granulocytes. Therefore, LTA represents a novel and promising agent capable of enhancing myocardial tolerance to ischemia/reperfusion injury.
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PMID:Lipoteichoic acid induces delayed protection in the rat heart: A comparison with endotoxin. 1084 67

Abdominal sepsis and septic shock are still major causes of mortality in intensive care units (ICU). Acute renal failure (ARF) is one of the hallmarks encountered in septic shock. The pathophysiological alterations leading to ARF are poorly understood. A novel murine model of polymicrobial sepsis (colon ascendens stent peritonitis [CASP]) was used to investigate functional renal parameters, renal chemokine transcription levels, and recruitment of inflammatory leukocytes in septic ARF. CASP was induced by inserting a 14-gauge stent into the colon ascendens of C57BL/6 mice, generating a septic focus resulting in polymicrobial sepsis. Mice were monitored for urine output and serum azotemia. Kidneys were harvested for analysis of leukocyte infiltration by immunohistochemistry and chemokine gene expression by RNase protection assay (3, 6, 12, and 18 h). CASP, but not sham-CASP, resulted in anuria immediately after surgery and in elevated serum creatinine and BUN detected 18 h after CASP surgery, confirming acute renal failure. Progressive induction of chemokine gene expression was observed for IP-10, MIP-2, MIP-1alpha, MIP-1beta, MCP-1, and RANTES peaking at 12 h with subsequent decrease. Immunohistochemistry revealed an accumulation of neutrophils and monocytes which had adhered to the renal vascular endothelium. Thus, acute renal failure in sepsis is accompanied by a marked upregulation of chemokines of the CC and CXC group within the kidney.
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PMID:Massive chemokine transcription in acute renal failure due to polymicrobial sepsis. 1094 65

The gene FLT1 produces at least two transcripts from a common transcription start site: full-length Flt1 contains 30 exons encoding a membrane-bound VEGF receptor; soluble Flt1 (sFlt1) shares the first 13 exons but utilizes poly(A) signal sequences within intron 13 to create a transcript that lacks downstream exons. To address the mechanisms that regulate human sFlt1, we mapped the 3' end of sFlt1 mRNA and defined the full extent of its 3' untranslated region (UTR). We identified a 3.2 Kb sFlt1 transcript that is cleaved within an alternatively spliced exon downstream of exon 14 and is predicted to encode a C-terminal variant of sFlt1 with an unusual polyserine tail. sFlt1 mRNA cleavage sites within intron 13 were identified in human placenta and in vascular endothelium by ribonuclease protection assay (RPA). A proximal and two distal mRNA cleavage sites were identified by RPA downstream of consensus polyadenylation signals that create variant transcripts with a 3' UTR ranging from 30 bases to approximately 4 Kb. Northern blot analysis and 3' rapid amplification of cDNA ends (RACE) in placenta confirmed the existence of distal intronic sFlt1 cleavage sites that give rise to a sFlt1 transcript of approximately 7 Kb. The identity of the distal signal sequences were then confirmed by mutagenesis of putative signal elements in a polyadenylation reporter assay. We demonstrate the heterogeneity of human sFlt1 that arises from alternate splicing and from alternative polyadenylation directed by strong intronic poly(A) signal sequences leading to C-terminal variants and to an sFlt1 transcript with a large 3' UTR containing several AU rich elements and poly(U) regions that may regulate mRNA stability.
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PMID:Intronic polyadenylation signal sequences and alternate splicing generate human soluble Flt1 variants and regulate the abundance of soluble Flt1 in the placenta. 1761 62


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