Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.26.9 (ribonuclease)
 6,589 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hormones can regulate the expression of their own receptor. We have examined whether adrenalectomy (ADX) and hormone replacement by physiological doses of aldosterone or dexamethasone could modulate the expression of glucocorticoid receptor (GR) or mineralocorticoid receptor (MR) at the mRNA level in the rat kidney, distal colon, and heart. Adult rats were adrenalectomized and received or did not receive an infusion of aldosterone (5 micrograms.100 g-1.day-1) or dexamethasone (10 micrograms.100 g-1.day-1). No significant change in steady-state levels of both MR and GR mRNA was detectable by using ribonuclease (RNase) protection assay (RPA) after either ADX or hormone replacement. Because the kidney is heterogeneous with regard to MR expression, RPA was adapted for measurements on microdissected nephron segments. GR mRNA is expressed at comparable levels all along the nephron, whereas MR mRNA is restricted to the distal nephron. No effect of ADX or GR and MR mRNA levels was detected in any nephron segment that was either aldosterone sensitive or insensitive. In situ hybridization confirmed the absence of corticosteroid-dependent modulation of MR mRNA in all kidney cell types. We conclude that variations of corticosteroid status do not affect MR and GR mRNA steady-state levels in heart, colon, and kidney and thus do not participate to the functional adaptations that are known to depend on hormonal status.
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PMID:Corticosteroid receptor mRNA expression is unaffected by corticosteroids in rat kidney, heart, and colon. 896 34

1. The effect of endogenous glucocorticoid hormones on the expression of rat B(1) receptors was examined by means of molecular and pharmacological functional approaches. 2. Rats were adrenalectomized (ADX), and 7 days after this procedure the intradermal injection of B(1) receptor agonist des-Arg(9)-BK produced a significant increase in the paw volume, while only a weak effect was observed in sham-operated animals. A similar increase in the contractile responses mediated by B(1) agonist des-Arg(9)-BK was also observed in the rat portal vein in vitro. 3. Chemical ADX performed with mitotane (a drug that reduces corticosteroid synthesis) produced essentially the same up-regulation of B(1) receptors as that observed in ADX rats. 4. The modulation of B(1) receptor expression was evaluated by ribonuclease protection assay, employing mRNA obtained from the lungs and paw of ADX rats. 5. Additionally, both paw oedema and contraction of portal vein mediated by B(1) agonist des-Arg(9)-BK in ADX rats, were markedly inhibited by treatment with dexamethasone, or COX-2 inhibitor meloxican, or with the NF-kappaB inhibitor PDTC. Interestingly, the same degree of inhibition was achieved when the animals were treated with a combination of submaximal doses of dexamethasone and PDTC. 6. The involvement of NF-kappaB pathway was further confirmed by mobility shift assay using nuclear extracts from lung, paw and heart of ADX rats. It was also confirmed that the treatment of ADX rats with dexamethasone, PDTC or dexamethasone plus PDTC completely inhibit NF-kappaB activation caused by absence of endogenous glucucorticoid. 7. Together, the results of the present study provide, for the first time, molecular and pharmacological evidence showing that B(1) kinin receptor expression can be regulated through endogenous glucocorticoids by a mechanism dependent on NF-kappaB pathway. Clinical significance of the present findings stem from evidence showing the importance of B(1) kinin receptors in the mediation of inflammatory and pain related responses.
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PMID:Molecular and pharmacological evidence for modulation of kinin B(1) receptor expression by endogenous glucocorticoids hormones in rats. 1115 7

Removal of adrenal steroids by adrenalectomy (ADX) slows or reverses the development of many forms of obesity in rodents, including those that are leptin or leptin receptor deficient. Obesity is associated with hyperleptinemia and leptin resistance. We hypothesized that glucocorticoids impair leptin receptor signaling and that removal thereof would activate the Janus kinase (JAK)-signal transducers and activators of transcription (STAT) signaling pathway. The inhibitory effect of leptin (2.5 microg icv) on food intake was enhanced in ADX rats. A combination of ribonuclease protection assays, RT-PCR, Western blots, and mobility shift assays was used to evaluate the leptin signaling pathway in whole hypothalami from sham-operated, ADX and corticosterone-replaced ADX (ADX-R) Sprague-Dawley rats that were treated acutely with either saline vehicle or leptin intracerebroventricularly. ADX increased the expression of leptin receptor mRNA, increased STAT-3 mRNA and protein levels, induced constitutive STAT-3 phosphorylation and DNA binding activity, and also reduced suppressor of cytokine signaling-3 (SOCS-3) mRNA and protein levels. ADX and leptin treatment increased STAT-3 phosphorylation, but with no concomitant increase in DNA binding activity. Leptin and ADX decreased NPY mRNA expression, but their combination did not further decrease NPY mRNA. Corticosterone supplementation of ADX rats partially reversed many of these effects. In conclusion, ADX through activation of STAT-3 and inhibition of SOCS-3 activates the JAK-STAT signaling pathway. These effects most probably explain the ability to prevent the development of obesity by removal of adrenal steroids.
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PMID:Constitutive activation of STAT-3 and downregulation of SOCS-3 expression induced by adrenalectomy. 1170 92

Darkness rapidly induces a decline in the stability and translation of the pea Ferredoxin-1 (Fed-1) mRNA in transgenic tobacco. Direct half-life measurement showed that mutation of the (CAUU)4 stabilizes Fed-1 mRNA in the dark. (CAUU)1, a feature more common in plant 5' UTRs than (CAUU)4, confers slight light-responsive mRNA accumulation. At least three but less than 11 CAUU repeats near the 5' end of the 5' UTR are required for full light-responsive accumulation. Furthermore, 26 nt of the 5' UTR, including the (CAUU)4 repeat, is sufficient to confer a significant approximately 2.5-fold increase in light-regulated mRNA accumulation when fused to the 5' end of a heterologous plant mRNA. A mutation of the (CAUU)4 repeat that compromises light-regulated mRNA stability changes in vitro the accessibility of the region to ribonuclease V1 and ribonuclease A suggesting the geometry formed by the repeat may be important for instability. Finally, dark-induced Fed-1 mRNA instability occurs even when most of the mRNA is retained on polyribosomes, and thus is likely an independent event regulated by darkness.
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PMID:The Fed-1 (CAUU)4 element is a 5' UTR dark-responsive mRNA instability element that functions independently of dark-induced polyribosome dissociation. 1580 13

Clustered regularly interspaced short palindromic repeats (CRISPRs) together with the associated CAS proteins protect microbial cells from invasion by foreign genetic elements using presently unknown molecular mechanisms. All CRISPR systems contain proteins of the CAS2 family, suggesting that these uncharacterized proteins play a central role in this process. Here we show that the CAS2 proteins represent a novel family of endoribonucleases. Six purified CAS2 proteins from diverse organisms cleaved single-stranded RNAs preferentially within U-rich regions. A representative CAS2 enzyme, SSO1404 from Sulfolobus solfataricus, cleaved the phosphodiester linkage on the 3'-side and generated 5'-phosphate- and 3'-hydroxyl-terminated oligonucleotides. The crystal structure of SSO1404 was solved at 1.6A resolution revealing the first ribonuclease with a ferredoxin-like fold. Mutagenesis of SSO1404 identified six residues (Tyr-9, Asp-10, Arg-17, Arg-19, Arg-31, and Phe-37) that are important for enzymatic activity and suggested that Asp-10 might be the principal catalytic residue. Thus, CAS2 proteins are sequence-specific endoribonucleases, and we propose that their role in the CRISPR-mediated anti-phage defense might involve degradation of phage or cellular mRNAs.
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PMID:A novel family of sequence-specific endoribonucleases associated with the clustered regularly interspaced short palindromic repeats. 1848 76