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)

To determine the organ distribution of production of the three endothelin (ET) isopeptides, we have developed three ribonuclease protection assays specific for the messenger RNAs (mRNAs) of rat ETs 1, 2, and 3.12 organs from adult Sprague-Dawley rats were examined: heart, lung, liver, spleen, kidney, stomach, small intestine, large intestine, testis, muscle, salivary gland, and brain. The mRNA for ET1 was five times more abundant in the lung than in any other organ studied, moderate expression was seen in the large intestine, and lower levels of mRNA were detected in each of the other organs examined. ET2 was expressed at high level in both large and small intestine and at low level in stomach, muscle, and heart, but ET2 mRNA could not be detected elsewhere. ET3 mRNA was found in all organs, particularly in small intestine, lung, kidney, and large intestine. Because of reports suggesting that ETs might be involved in the hypoperfusion and hypofiltration observed in postischemic kidneys, we have also studied levels of mRNA in kidneys that had previously been subjected to 25 or 45 min of clamping of the renal pedicle. At 6 h after 45 min of ischemia, ET1 mRNA increased to a peak of 421 +/- 69% (mean +/- SEM, n = 3) of that in a standard renal RNA preparation. By contrast, ET3 mRNA decreased in the postischemic organ, falling to a value of 19 +/- 2% of standard at the same time point. The effects of ischemia on ET1 and ET3 mRNAs were long-lasting, with elevation of ET1 and depression of ET3 persisting for days. ET2 mRNA remained undetectable throughout. These findings (a) support a role for ET1 in postischemic renal vascular phenomena and (b) demonstrate a situation in which the expression of ET isoforms is clearly subject to differential regulation.
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PMID:Organ distribution of the three rat endothelin messenger RNAs and the effects of ischemia on renal gene expression. 152 10

Endothelins (ETs) 1 and 3 are expressed in the rat kidney, but the factors that regulate this expression remain unknown. To try to understand what these might be, we have measured the renal levels of ET-1 and ET-3 mRNAs by the ribonuclease protection-assay technique after a number of clearly defined renal/hemodynamic insults. 1) Six hours after the induction of hemorrhagic anemia and hypotension, there was a threefold increase in ET-1 mRNA and a simultaneous threefold decrease in ET-3 mRNA. This indicates that, in this situation, these two ET isoforms are differentially controlled and emphasizes the need for assay techniques capable of distinguishing between them. 2) One day after application of a 0.2-mm clip to the left renal artery, there was a > 2.5-fold induction of ET-1 mRNA in that kidney, which persisted for 10 days. A smaller rise in ET-1 mRNA was seen in the contralateral organ. After 2 days, ET-3 mRNA levels were reduced by approximately 50% in the clipped organ. Both ramipril (an angiotensin-converting enzyme inhibitor, 7.5 mg/kg daily) and bosentan (a nonselective ET receptor antagonist, 100 mg/kg daily) substantially reduced the elevation in ET-1 mRNA seen in the clipped kidney after 2 days, suggesting that the generation of angiotensin II and the action of ET itself are involved in the mechanism by which clipping stimulates ET-1 expression. By contrast, ramipril, but not bosentan, prevented the reduction in ET-3 mRNA levels. 3) Renal denervation, dietary salt restriction, or diuretic treatment (furosemide) did not alter renal expression of ET-1 or ET-3.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Expression of endothelins 1 and 3 in the rat kidney. 748 37

We hypothesize that poly (ADP-ribosyl)ation, that is, poly (ADP-ribose) polymerase (PARP)-dependent transfer of ADP-ribose moieties from NAD to nuclear proteins, plays a role in diabetic nephropathy. We evaluated whether PARP activation is present and whether two unrelated PARP inhibitors, 3-aminobenzamide (ABA) and 1,5-isoquinolinediol (ISO), counteract overexpression of endothelin-1 (ET-1) and ET receptors in the renal cortex in short-term diabetes. The studies were performed in control rats and streptozotocin-diabetic rats treated with/without ABA or ISO (30 and 3 mg x kg(-1) x day(-1), intraperitoneally, for 2 weeks after 2 weeks of diabetes). Poly (ADP-ribose) immunoreactivity was increased in tubuli, but not glomeruli, of diabetic rats and this increase was corrected by ISO, whereas ABA had a weaker effect. ET-1 concentration (ELISA) was increased in diabetic rats, and this elevation was blunted by ISO. ET-1, ET(A), and ET(B) mRNA (ribonuclease protection assay), but not ET-3 mRNA (RT/PCR), abundance was increased in diabetic rats, and three variables were, at least, partially corrected by ISO. ABA produced a trend towards normalization of ET-1 concentration and ET-1, ET(A), and ET(B) mRNA abundance, but the differences with untreated diabetic group were not significant. Poly(ADP-ribosyl)ation is involved in diabetes-induced renal overexpression of ET-1 and ET receptors. PARP inhibitors could provide a novel therapeutic approach for diabetic complications including nephropathy, and other diseases that involve the endothelin system.
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PMID:Diabetes-induced overexpression of endothelin-1 and endothelin receptors in the rat renal cortex is mediated via poly(ADP-ribose) polymerase activation. 1282 90