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:3.1.27.5 (RNase)
17,967 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sodium (Na) channel cDNAs were synthesized from RNA isolated from rat brain, cardiac muscle, and skeletal muscle. Partial cDNAs coding for the largest cytoplasmic loop of the Na channel were amplified with PCR. Sequence analysis of these cDNAs revealed that Na channel cDNAs originally described as brain genes were also expressed in both cardiac and skeletal muscle. Some of these cDNAs were isoforms that differed by insertions or deletions and can be explained by alternative choices of a 5' splice site. Southern blot analysis of genomic DNA confirmed the presence of introns in this region of the gene. Transcripts of multiple isoforms were detected with RNase protection in brain, heart, and skeletal muscle. Several conclusions can be drawn from the data. (1) Some rat sodium channel genes are transcribed in all excitable tissues studied here: brain, cardiac muscle, and skeletal muscle. (2) Each of these three tissues expresses multiple sodium channel genes. (3) Alternative splicing of sodium channel transcripts occurs in these tissues. (4) Expression of multiple genes and alternative splicing of the transcripts is responsible for at least seven different sodium channel mRNAs in skeletal muscle.
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PMID:Alternatively spliced sodium channel transcripts in brain and muscle. 131 93

To study the mechanisms which mediate the transcriptional activation of cardiac genes during alpha adrenergic stimulation, the present study examined the regulated expression of three cardiac genes, a ventricular embryonic gene (atrial natriuretic factor, ANF), a constitutively expressed contractile protein gene (cardiac MLC-2), and a cardiac sodium channel gene. alpha 1-Adrenergic stimulation activates the expression and release of ANF from neonatal ventricular cells. As assessed by RNase protection analyses, treatment with alpha-adrenergic agonists increases the steady-state levels of ANF mRNA by greater than 15-fold. However, a rat cardiac sodium channel gene mRNA is not induced, indicating that alpha-adrenergic stimulation does not lead to an increase in the expression of all cardiac genes. Studies employing a series of rat ANF luciferase and rat MLC-2 luciferase fusion genes identify 315- and 92-base pair cis regulatory sequences within an embryonic gene (ANF) and a constitutively expressed contractile protein gene (MLC-2), respectively, which mediate alpha-adrenergic-inducible gene expression. Transfection of various ANF luciferase reporters into neonatal rat ventricular cells demonstrated that upstream sequences which mediate tissue-specific expression (-3003 to -638) can be segregated from those responsible for inducibility. The lack of inducibility of a cardiac Na+ channel gene, and the segregation of ANF gene sequences which mediate cardiac specific from those which mediate inducible expression, provides further insight into the relationship between muscle-specific and inducible expression during cardiac myocyte hypertrophy. Based on these results, a testable model is proposed for the induction of embryonic cardiac genes and constitutively expressed contractile protein genes and the noninducibility of a subset of cardiac genes during alpha-adrenergic stimulation of neonatal rat ventricular cells.
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PMID:Co-regulation of the atrial natriuretic factor and cardiac myosin light chain-2 genes during alpha-adrenergic stimulation of neonatal rat ventricular cells. Identification of cis sequences within an embryonic and a constitutive contractile protein gene which mediate inducible expression. 185 Apr 19

We have recently described the cloning and functional expression of a new sodium channel subtype, microI, isolated from a denervated rat skeletal muscle cDNA library. In studies described here, we have used RNase protection and Northern blot analyses to examine the expression of microI mRNA in different tissues and in neonatal, adult, and adult denervated muscle. We found that microI transcripts were not expressed in brain or heart, or in the myogenic cell line L6, even after differentiation to myotubes. Transcripts for microI were present at low levels in neonatal skeletal muscle and increased to maximum levels in adult tissue, paralleling the expression of tetrodotoxin (TTX)-sensitive sodium currents. Surprisingly, denervation of adult muscle was also followed by a rise in microI mRNA, at a time when TTX-insensitive currents reappear. These results show that expression of this channel subtype is regulated by tissue type, development, and innervation.
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PMID:Regulation of muscle sodium channel transcripts during development and in response to denervation. 217 78

Tetrodotoxin-insensitive (TTX-I) sodium currents have been recorded from newborn and adult rat sensory neurons, but the sodium channel gene(s) responsible for the TTX-I current are unknown. Because SkM2, one of six voltage-sensitive sodium channel genes cloned from rat, encodes the only cloned channel that is relatively resistant to tetrodotoxin, we sought to test whether the TTX-I current in rat sensory neurons is due to the SkM2 channel. We hypothesized that the TTX-I current might be generated from (1) an RNA splicing variant of SkM2, (2) post-translational modification of the SkM2 protein, or (3) interaction with alternate additional channel subunits. SkM2 mRNA expression was examined in newborn rat dorsal root ganglia (DRG) by RNase protection assay. No SkM2 expression was detected. Therefore, we conclude that the TTX-I sodium current in DRG is unlikely to result from the expression of the SkM2 gene.
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PMID:The tetrodotoxin-insensitive sodium current in rat dorsal root ganglia is unlikely to involve the expression of the tetrodotoxin-resistant sodium channel, SkM2. 756 68

The amiloride-sensitive epithelial sodium channel (ENAC) consists of at least three subunits, alpha, beta, and gamma. Sodium conductance occurs when only the alpha subunit is expressed in Xenopus oocytes, but it is greatly enhanced by coexpression of all three subunits. All three subunits have two transmembrane domains. Whether the amiloride binding site exists in the extracellular portion or a transmembrane domain has not been established. Using reverse transcription-polymerase chain reaction in rat taste tissues, we have identified two alternatively spliced transcripts of ENAC (alpha ENACa and alpha ENACb) with deletions of nucleotides that introduce a premature stop codon and may result in proteins shortened by 199 and 216 amino acids, respectively, at the carboxyl terminus. Genomic Southern blots indicate that a single gene accounts for alpha ENAC and the alternatively spliced variants. Reverse transcription-polymerase chain reaction and RNase protection assays demonstrate that alpha ENACa is expressed to a lesser extent than alpha ENAC in kidney, lung, and taste tissues. alpha ENACa differs from alpha ENAC by a deletion in the second transmembrane domain. Despite this deletion, alpha ENACa expression in transfected human embryonic kidney 293 cells or CV-1 cells augments [3H]phenamil binding. The [3H]phenamil binding of alpha ENACa resembles that of alpha ENAC, being inhibited more potently by phenamil (Kd = 65 nM) than amiloride. Unlike alpha ENAC, expression of alpha ENACa in Xenopus oocytes fails to generate amiloride-sensitive Na+ or Li+ currents. These results suggest that the amiloride binding site resides on the extracellular loop of the alpha subunit of ENAC and not the putative second transmembrane domain, which forms a channel pore. Heterogeneity in alpha ENAC isoforms may contribute to the complexity of multimeric structures and functional variation of ENAC.
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PMID:Alternatively spliced forms of the alpha subunit of the epithelial sodium channel: distinct sites for amiloride binding and channel pore. 760 52

A novel, voltage-gated sodium channel cDNA, designated NaCh6, has been isolated from the rat central and peripheral nervous systems. RNase protection assays showed that NaCh6 is highly expressed in the brain, and NaCh6 mRNA is as abundant or more abundant than the mRNAs for previously identified rat brain sodium channels. In situ hybridization demonstrated that a wide variety of neurons express NaCh6, including motor neurons in the brainstem and spinal cord, cerebellar granule cells, and pyramidal and granule cells of the hippocampus. RT-PCR and/or in situ hybridization showed that astrocytes and Schwann cells express NaCh6. Thus, this sodium channel is broadly distributed throughout the nervous system and is shown to be expressed in both neurons and glial cells.
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PMID:A novel, abundant sodium channel expressed in neurons and glia. 775 6

The inherited diseases hyperkalemic periodic paralysis and paramyotonia congenita are caused by mutations in the adult skeletal muscle sodium channel gene. To determine if differences in the expression patterns of the adult and cardiac/fetal sodium channel genes could explain some clinical features of these disorders, we developed a novel mRNA quantitation strategy called quantitative multiplex fluorescent polymerase chain reaction (QMF-PCR). This assay tests the relative levels of multiple mRNA species simultaneously using automated sequenators. We show validation of this method by competitive-PCR and RNase protection. Developmental studies of sodium channel mRNAs in humans and mice by QMF-PCR showed that the adult sodium channel mRNA quickly increased, while the cardiac/fetal sodium channel mRNA slowly decreased similarly in both limb and diaphragm muscle. We find that the adult sodium channel gene expression is predominant in fetal and neonatal muscle of both humans and mice: adult isoform mRNA concentration in fetal muscle was 8.4 x 10(-6) micrograms/micrograms of total RNA; cardiac/fetal isoform mRNA was 2.0 x 10(-6) micrograms/micrograms; and actin mRNA was 3.4 x 10(-3) micrograms/micrograms. Our results suggest that differential sodium channel gene expression correlates with age of onset of disease, but not with diaphragm involvement, in patients with hyperkalemic periodic paralysis.
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PMID:Pathophysiology of sodium channelopathies. Studies of sodium channel expression by quantitative multiplex fluorescence polymerase chain reaction. 803 5

Nerve growth factor (NGF) plays an important role in the development of the nervous system, and there is considerable interest in understanding the molecular mechanisms underlying its effects on neuronal differentiation. To determine if the activity of proteins of the ras gene family is necessary for the NGF-mediated induction of sodium channel expression in pheochromocytoma (PC12) cells, sodium channel expression was analyzed in PC12 sublines stably overexpressing the dominant inhibitory mutant c-Ha-ras(Asn-17). Northern blot analysis, RNase protection assays, and whole-cell patch clamp recordings indicate that the NGF-mediated increase in type II sodium channel mRNA and sodium current density can occur independent of ras activity and by doing so provide strong evidence for the importance of ras-independent mechanisms in NGF-mediated neuronal differentiation.
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PMID:ras-independent induction of rat brain type II sodium channel expression in nerve growth factor-treated PC12 cells. 822 7

Three subunits (alpha, beta, gamma) of the amiloride-sensitive epithelial sodium channel have been recently characterized. The channel subunits have significant homologies with the Caenorhabditis elegans mec-4, mec-10 and deg-1 genes, which are involved in control of cell volume and mecanotransduction. These subunits are coexpressed at equivalent levels in the renal collecting duct and the distal colon epithelium which are high resistance sodium transporting epithelia. We have investigated whether these subunits were expressed, at the mRNA level, in transporting as well as non transporting epithelial cells of rat skin. In full-thickness abdominal skin only alpha and gamma subunit mRNAs were detected, while all three subunit mRNAs were present in sole skin, as demonstrated by RNase-protection assay. Furthermore, the level of expression of each subunit varied with the epithelial cell type as demonstrated by in situ hybridization: epidermal and follicular keratinocytes express mostly alpha and gamma subunits (while beta was low); a prevalence of beta and gamma was observed in sweat glands. Thus, it appeared that two out of the three subunit mRNAs predominated in each epithelial structure. In addition, mRNAs of the alpha, beta and gamma subunits of the amiloride-sensitive sodium channel were expressed at a higher level in large suprabasal epidermal keratinocytes (which undergo terminal differentiation) than in small proliferative basal keratinocytes.
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PMID:Differential expression of epithelial sodium channel subunit mRNAs in rat skin. 883 61

The efficacy of steroid therapy for the treatment of otitis media in children remains controversial, and a putative modulation of the middle ear epithelial function has to be demonstrated. Using the MESV cell line, short-circuit current (ISC) technique was used to evaluate changes in ion transport induced by glucocorticoids. Dexamethasone (DXM) produced a dose- and time-dependent increase in ISC in MESV cells. This effect was inhibited by specific glucocorticoid antagonist (RU-38486) and was related to a sodium transport, since the DXM-induced increase in ISC could be prevented or abolished i) by apical addition of the specific Na+ channel inhibitor benzamil; or ii) by substitution of sodium with N-Methyl-glucamine in the incubation medium. RNase protection assay revealed that DXM increased the expression of the alpha subunit sodium channel mRNA, which changes paralleled the modulation of ion transport. These data demonstrate that steroids up-regulate the trans-epithelial sodium transport in the middle ear epithelium. As far as these experimental data can be extrapolated to the in vivo situation, a component of the beneficial effect of steroid therapy for the treatment of otitis media may result from a corticosteroid-induced improvement in fluid clearance from the middle ear.
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PMID:Modulation of middle ear epithelial function by steroids: clinical relevance. 910 67


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