Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.27.4 (ribonuclease)
 6,621 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chronic ethanol exposure and subsequent withdrawal are known to change NMDA receptor activity. This study examined the effects of chronic ethanol administration and withdrawal on the expression of several NMDA receptor subunit and splice variant mRNAs in the rat cerebral cortex. Ethanol dependence was induced by ethanol vapour exposure. To delineate between seizure-induced changes in expression during withdrawal and those due to withdrawal per se, another group of naive rats was treated with pentylenetetrazol (PTZ) injection (30 mg/kg, i.p.). RNA samples from the cortices of chronically treated and withdrawing animals were compared to those from pair-fed controls. Changes in NMDA receptor mRNA expression were determined using ribonuclease protection assays targetting the NR2A, -2B, -2C and NR1-pan subunits as well as the three alternatively spliced NR1 inserts (NR1-pan describes all the known NR1 splice variants generated from the 5' insert and the two 3' inserts). The ratio of NR1 mRNA incorporating the 5' insert vs. that lacking it was decreased during ethanol exposure and up to 48 h after withdrawal. NR2B mRNA expression was elevated during exposure, but returned to control levels 18 h after withdrawal. Levels of NR2A, NR2C, NR1-pan and both 3' NR1 insert mRNAs from the ethanol-treated groups did not alter compared with the pair-fed control group. No changes in the level of any NMDA receptor subunit mRNA was detected in the PTZ-treated animals. These data support the hypothesis that changes in NMDA receptor subunit composition may underlie a neuronal adaptation to the chronic ethanol-inhibition and may therefore be important in the precipitation of withdrawal hyperactivity.
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PMID:Chronic ethanol exposure and withdrawal influence NMDA receptor subunit and splice variant mRNA expression in the rat cerebral cortex. 1008 58

The N-methyl-D-aspartate (NMDA) subtype of glutamate receptors plays a key role in synaptic transmission, synaptic plasticity, synaptogenesis, and excitotoxicity in the mammalian central nervous system. The NMDA receptor channel is formed from two gene products from two glutamate receptor subunit families, termed NR1 and NR2. Although the subunit composition of native NMDA receptors is incompletely understood, electrophysiological studies using recombinant receptors suggest that functional NMDA receptors consist of heteromers containing combinations of NR1, which is essential for channel activity, and NR2, which modulates the properties of the channels. The lack of agonists or antagonists selective for a given subunit of NMDA receptors has made it difficult to understand the subunit expression, subunit composition, and posttranslational modification mechanisms of native NMDA receptors. Therefore, most studies on NMDA receptors that examine regional expression and ontogeny have been focused at the level of the mRNAs encoding the different subunits using northern blotting, ribonuclease protection, and in situ hybridization techniques. However, the data from these studies do not provide clear information about the resultant subunit protein. To directly examine the protein product of the NMDA receptor subunit genes, the development of subunit-specific antibodies using peptides and fusion proteins has provided a good approach for localizing, quantifying, and characterizing the receptor subunits in tissues and transfected cell lines, and to study the subunit composition and the functional effects of posttranslational processing of the NMDA subunits, particularly the phosphorylation profiles of NMDA glutamate receptors.
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PMID:Biochemical studies of the structure and function of the N-methyl-D-aspartate subtype of glutamate receptors. 1037 67

Increasing evidence based on pharmacological and genetic studies suggests that retinoid signaling plays an important role in developmental control of striatal neurons. In the present report, we screened for genes that might be regulated by retinoids in the developing striatum. We cultured tissue explants from the lateral ganglionic eminence (striatal primordium), and for regional comparison, its adjacent structures of the cerebral cortex and the medial ganglionic eminence in embryonic day 15 rat telencephalon. Using the ribonuclease protection assay, we found that both all-trans retinoic acid and 9-cis retinoic acid significantly up-regulated dopamine D1 receptor, heterotrimeric G protein olfactory, adenylyl cyclase type V and dopamine- and cyclic adenosine 3':5'-monophosphate-regulated phosphoprotein mRNAs in the lateral ganglionic eminence culture. By contrast, neither all-trans retinoic acid nor 9-cis retinoic acid significantly altered D1 receptor, heterotrimeric G protein olfactory, adenylyl cyclase type V and dopamine- and cyclic adenosine 3':5'-monophosphate-regulated phosphoprotein mRNAs in the cortical and the medial ganglionic eminence cultures except that D1 receptor mRNA was dramatically induced in the medial ganglionic eminence by retinoic acid treatments. To test whether the induction of multiple dopamine signaling molecules in the lateral ganglionic eminence was due to a general enhancement of neuronal differentiation by retinoic acid, we assayed the effects of retinoic acid on other differentiation markers, including glutamate decarboxylase 65, NR1 subunit of glutamate NMDA receptor and microtubule-associated protein-2. None of these genes were significantly altered by retinoic acid treatments in the lateral ganglionic eminence culture, indicating the specificity of gene regulation by retinoic acid signaling. As D1 receptor, heterotrimeric G protein olfactory, adenylyl cyclase type V and dopamine- and cyclic adenosine 3':5'-monophosphate-regulated phosphoprotein are important molecules involved in propagation of striatal dopamine neurotransmission, our study raises the hypothesis that retinoid signaling may coordinately activate the transcriptional program that is associated with the dopamine signaling pathway in developing striatal neurons. Such coordinate regulation by retinoids may be part of the mechanisms by which the complex yet highly organized neurochemical constituents of the striatum are established during development.
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PMID:Regulation of multiple dopamine signal transduction molecules by retinoids in the developing striatum. 1593 42

Recently we showed that the level of mitochondrial mRNA was decreased prior to neuronal death induced by glutamate. As the level of mRNA is regulated by ribonuclease (RNase), we examined RNase activity and its expression in the primary cultures of cortical neurons after glutamate treatment in order to evaluate the involvement of RNase in glutamate-induced neuronal death. A 15-min exposure of the cultures to glutamate at the concentration of 100 microM produced marked neuronal damage (more than 70% of total cells) at 24-h post-exposure. Under the experimental conditions used, RNA degradation was definitely observed at a period of 4-12-h post-exposure, a time when no damage was seen in the neurons. Glutamate-induced RNA degradation was completely prevented by the N-methyl-d-aspartic acid (NMDA) receptor channel blocker MK-801 or the NR2B-containing NMDA receptor antagonist ifenprodil. Glutamate exposure produced enhanced expression of RNase L at least 2-12h later, which was absolutely abolished by MK-801. However, no significant change was seen in the level of RNase H1 mRNA at any time point post-glutamate treatment. Immunocytochemical studies revealed that RNase L expressed in response to glutamate was localized within the nucleus, mitochondria, and cytoplasm in the neurons. Taken together, our data suggest that expression of RNase L is a signal generated by NMDA receptor in cortical neurons. RNase L expression and RNA degradation may be events that cause neuronal damage induced by NMDA receptor activation.
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PMID:Enhanced expression of RNase L as a novel intracellular signal generated by NMDA receptors in mouse cortical neurons. 1858 18

Differentiated P19 cells naturally express N-methyl-D-aspartate (NMDA) receptors and serve as a good in vitro model system with which to study NMDA receptor regulation. Here we examined expression of NR1 mRNA binding trans-acting proteins and NR1 splice variants in P19 cells. After exposure to retinoic acid, P19 cells were differentiated for 2, 4, 6, and 8 days in vitro (DIV). Total RNA and protein extracts from differentiated P19 cells were utilized to examine NR1 and NR2B expression. A steady increase in NR1 and NR2B mRNA and protein levels was observed with respect to days of differentiation. NR2B mRNA was detected within 2 DIV. However, NR2B protein appeared only at 4 DIV. By contrast, minimal expression of NR1 mRNA could be detected in undifferentiated P19 cells, whereas NR1 protein was detected at 4 DIV. RT-PCR analysis identified expression of four of eight full-length NR1 splice variants, similar to the expression pattern seen in fetal cortical neurons (FCN). These data were confirmed by ribonuclease protection assays. RNA gel shift assays and Northwestern analysis revealed the expression of NR1 mRNA binding trans-acting proteins in P19 neurons comparable to those expressed in FCN. RNA super gel shift assays confirmed the presence of the NR1 mRNA binding trans-acting protein GIIbeta in the NR1-3'UTR-P19 protein complex. Levels of GIIbeta polypeptide increased with increase in days of differentiation. Taken together, our data demonstrate that differentiated P19 cells are comparable to FCN and hence provide an excellent in vitro model for studying NR1 mRNA regulation at the posttranscriptional level.
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PMID:Differentiated P19 cells express N-methyl-D-aspartate receptor 1 mRNA binding trans-acting proteins and four N-methyl-D-aspartate receptor 1 splice variants comparable to those in cultured fetal cortical neurons. 1915 58