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 developmental regulation of rat brain-derived/Hep G2 glucose transporter gene expression was studied by means of Northern blot hybridization, using a rat brain glucose transporter cDNA probe, in order to directly quantify steady state glucose transporter mRNA levels. The results obtained showed different tissue-specific patterns of glucose transporter mRNA levels during ontogenesis; while in brain there was a sustained increase in the levels of the message from 20 days embryogenesis until 50 days postnatal, other organs such as heart, lung, liver, and muscle expressed maximal levels of the glucose transporter mRNA in 20-day fetuses and 1-day neonates, decreasing subsequently to very low levels. The relative expression of the glucose transporter mRNA in the different tissues, at both fetal and adult stages, was analyzed using a solution hybridization-RNase protection assay. This approach revealed that, while the heart expresses the highest levels of glucose transporter mRNA at 20 days of fetal life, the brain shows the highest levels at the adult stage. These results indicate a tissue-specific ontogenic pattern of glucose transporter gene expression, suggesting a developmental role for this glucose transporter gene product.
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PMID:Developmental regulation of rat brain/Hep G2 glucose transporter gene expression. 271 Jan 34

Thyroid hormone (TH) plays a critical role in normal cerebellar development. However, the molecular mechanisms of TH action in the developing cerebellum are not fully understood. This action could be exerted in part through brain-derived neurotropic factor (BDNF), as cerebellar BDNF messenger RNA (mRNA) expression is lower, and replacement of BDNF partially reverses the abnormal neurogenesis in the hypothyroid rat. The rat BDNF gene consists of four noncoding exons (exons I-IV), each of which is linked to a different promoter, and a protein-coding exon (exon V). To study promoter-specific regulation of the BDNF gene by TH, ribonuclease protection assay of each exon mRNA was performed using total developing rat cerebellar RNA. During cerebellar development, all exon mRNAs were detected, but with different expression patterns; among noncoding exon mRNAs, exon II mRNA was the most abundant. Daily TH replacement induced a 3-fold increase in exon II mRNA on postnatal day (P) 15. On P30, exon II mRNA was still much greater in the TH-replaced animal. Exon I mRNA was detected on P2 and P7. However, in contrast to exon II mRNA, TH treatment suppressed the expression of exon I mRNA on P2. Exon III and IV mRNAs were not detected on P2 and P7, but small amounts were observed starting on P15 in TH-replaced animals. They were not detected by P30 in hypothyroid animals. In contrast, in the cerebral cortex, although all exons are differentially regulated during development, the expression of each mRNA was not significantly altered by TH. These results indicate that TH regulates BDNF gene expression in a promoter-, developmental stage-, and brain region-specific manner, which may play an important role in region- and stage-specific regulation of brain development by TH.
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PMID:Promoter-specific regulation of the brain-derived neurotropic factor gene by thyroid hormone in the developing rat cerebellum. 1046 64

The BeAn strain of Theiler's murine encephalomyelitis virus (TMEV) persists in the CNS and produces a chronic inflammatory demyelinating disease that is an animal model for human multiple sclerosis (MS). The mechanisms leading to TMEV-induced demyelination are still under study but most likely involve both immune-mediated and virus induced damage to cells in the CNS, both depending on viral persistence. It is therefore important to identify the cells in which continued virus production is permitted. In this study, we looked at virus infection in primary astrocytes, microglia and oligodendrocytes, derived from brains of neonatal susceptible SJL/J mice. As evidenced by Western blots and immunocytochemistry, we were able to detect viral antigens in all these brain-derived cells. In addition, we extended the study to spinal cord tissues from mice suffering TMEV-induced disease. Immunohistochemistry staining with anti-TMEV sera and antibodies to specific cell markers detected viral antigens in all these cells. We then asked the question whether viral antigen present in these cells, particularly in microglia/macrophages, represented true viral replication or not. By using different techniques, including immunoprecipitation experiments and the very sensitive method of negative RNA detection through RNase protection assay, we show that both astrocytes and oligodendroglia permit de novo viral replication and viral protein synthesis but with only minimal cytopathic effects. Of these two cell types, astrocytes carry the brunt of viral replication. In microglia, on the other hand, viral replication is restricted since only minimal amounts of negative RNA copies can be demonstrated, while there are clear signs that some of these cells undergo apoptosis. These findings show that the main cell for viral replication is the astrocyte, rather than the microglia/macrophage. Most of the viral antigen present in macrophages, therefore, is probably the result of phagocytosis, rather than actual viral replication. In view of the demonstrated presence of viral replication in astrocytes and of great amounts of viral antigens in microglia/macrophages, it is possible that both types of cells act as antigen presenting cells during this immunopathological disease.
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PMID:Astrocytes, not microglia, are the main cells responsible for viral persistence in Theiler's murine encephalomyelitis virus infection leading to demyelination. 1202 Sep 50

Circulating B cells enter the CNS as part of normal immune surveillance and in pathologic states, including the common and disabling illness multiple sclerosis. However, little is known about the molecular mechanisms that mediate human B cell interaction with the specialized brain endothelial cells comprising the blood-brain barrier (BBB). We studied the molecular mechanisms that regulate the migration of normal human B cells purified ex vivo, across human adult brain-derived endothelial cells (HBECs). We found that B cells migrated across HBECs more efficiently than T cells from the same individuals. B cell migration was significantly inhibited by blocking Abs to the adhesion molecules ICAM-1 and VLA-4, but not VCAM-1, similar to the results previously reported for T cells. Blockade of the chemokines monocyte chemoattractant protein-1 and IL-8, but not RANTES or IFN-gamma-inducible protein-10, significantly inhibited B cell migration, and these results were correlated with the chemokine receptor expression of B cells measured by flow cytometry and by RNase protection assay. Tissue inhibitor of metalloproteinase-1, a natural inhibitor of matrix metalloproteinases, significantly decreased B cell migration across the HBECs. A comprehensive RT-PCR comparative analysis of all known matrix metalloproteinases and tissue inhibitors of metalloproteinases in human B and T cells revealed distinct profiles of expression of these molecules in the different cell subsets. Our results provide insights into the molecular mechanisms that underlie human B cell migration across the BBB. Furthermore, they identify potential common, and unique, therapeutic targets for limiting CNS B cell infiltration and predict how therapies currently developed to target T cell migration, such as anti-VLA-4 Abs, may impact on B cell trafficking.
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PMID:Determinants of human B cell migration across brain endothelial cells. 1270 26

Several lines of evidence suggest that various cofactors may be required for prion replication. PrP binds to polyanions, and RNAs were shown to promote the conversion of PrP(C) into PrP(Sc) in vitro. In the present study, we investigated strain-specific differences in RNA requirement during in vitro conversion and the potential role of RNA as a strain-specifying component of infectious prions. We found that RNase treatment impairs PrP(Sc)-converting activity of 9 murine prion strains by protein misfolding cyclic amplification (PMCA) in a strain-specific fashion. While the addition of RNA restored PMCA conversion efficiency, the effect of synthetic polynucleotides or DNA was strain dependent, showing a different promiscuity of prion strains in cofactor utilization. The biological properties of RML propagated by PMCA under RNA-depleted conditions were compared to those of brain-derived and PMCA material generated in the presence of RNA. Inoculation of RNA-depleted RML in Tga20 mice resulted in an increased incidence of a distinctive disease phenotype characterized by forelimb paresis. However, this abnormal phenotype was not conserved in wild-type mice or upon secondary transmission. Immunohistochemical and cell panel assay analyses of mouse brains did not reveal significant differences between mice injected with the different RML inocula. We conclude that replication under RNA-depleted conditions did not modify RML prion strain properties. Our study cannot, however, exclude small variations of RML properties that would explain the abnormal clinical phenotype observed. We hypothesize that RNA molecules may act as catalysts of prion replication and that variable capacities of distinct prion strains to utilize different cofactors may explain strain-specific dependency upon RNA.
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PMID:Strain-specific role of RNAs in prion replication. 2281 20