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:3.1.26.9 (ribonuclease)
6,589 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Feeding a lipogenic diet increases transcription and enhances processing of the rat hepatic messenger RNA (mRNA)-S14 gene. To determine the separate roles of insulin and increased glucose in these processes, we used the streptozotocin-induced diabetic rat model. Diabetes caused a reduction in mature mRNA-S14 in chow- and lipogenic diet-fed animals (P < 0.006 and P < 0.001, respectively). Insulin restored these levels to normal. Despite the known effects of insulin and carbohydrate on the transcription of this gene, we were unable to demonstrate significant changes in the nuclear proteins that bind to carbohydrate response regions. Yet, insulin restored the content of the mRNA by increasing the ratio of mature to precursor mRNA-S14. Insulin significantly increased this ratio (P < 0.0001) independent of diet and diabetes, further supporting the action of insulin on increasing processing from precursor to mature mRNA. The mechanism of the enhanced processing was studied by ribonuclease mapping and primer extension analysis. Ribonuclease mapping showed that lipogenic diet feeding increases the efficiency of processing at a step before formation of the branched form of the precursor mRNA. Taken together, our data demonstrate for the first time that insulin significantly enhances the efficiency of processing of a pre-mRNA.
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PMID:Insulin increases the processing efficiency of messenger ribonucleic acid-S14 nuclear precursor. 864 Nov 78

Nonenzymatic glycation (Maillard reaction) of long-lived proteins is a major contributor to the pathology of diabetes and possibly aging and Alzheimer's disease. We report here kinetic studies of the glycation of the model protein ribonuclease A by glucose and ribose leading to the formation of antigenic advanced glycation end products ("AGEs"), detectable by AGE-specific polyclonal antibodies, and pentosidine, an acid-stable fluorescent AGE. As anticipated, the kinetics of glycation by ribose were considerably faster than by glucose, and the rate of AGE formation initially increased with increasing sugar concentrations. However, ribose above 0.15 M appeared to paradoxically slow the kinetics of AGE formation, suggesting ribose inhibits the conversion of "early" Amadori rearrangement products to "late" AGEs and thus favors the accumulation of reactive Amadori intermediates. The facile isolation of such protein intermediates was achieved by an "interrupted glycation" protocol which free and reversibly bound (Schiff base) ribose was removed following a short (24h) initial incubation of 0.5 M ribose at 37 degrees C. The kinetics of buildup of the Amadori intermediates and the kinetics of their post-Amadori conversion to antigenic AGEs were independently studied. A rapid and reversible inhibition of the post-Amadori kinetics by free ribose was verified by direct re-addition of ribose to the isolated, sugar-free intermediate. The pH dependence of the kinetics of antigenic AGE formation from such intermediates was measured and exhibited an unusual bell-shaped profile over the pH range of 5.0-9.5 with a maximum near pH 8.0. Aminoguanidine, a pharmacological AGE inhibitor, was found to moderately or weakly inhibit antigenic AGE formation in such post- Amadori steps. The isolation of the glycated ribonuclease intermediate thus simplifies kinetic and mechanistic studies of AGE formation, permits AGE studies in the absence of complications arising from free or Schiff base bound sugar, and provides a novel methodology for evaluating the mechanism and efficacy of therapeutic agents that may inhibit AGE formation.
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PMID:Kinetics of nonenzymatic glycation of ribonuclease A leading to advanced glycation end products. Paradoxical inhibition by ribose leads to facile isolation of protein intermediate for rapid post-Amadori studies. 866 53

Ras associated with diabetes (Rad), a new ras-related GTPase, was recently identified by subtractive cloning as an mRNA in skeletal muscle that is overexpressed in NIDDM. To better understand its metabolic significance, we measured skeletal muscle Rad expression in well-characterized insulin sensitive (IS) and insulin resistant (IR) subjects with normal glucose tolerance and in untreated NIDDM patients. We found no differences in expression of Rad mRNA levels among IS, IR, and NIDDM groups using a ribonuclease protection assay (0.22 +/- 0.06, 0.13 +/- 0.01, and 0.16 +/- 0.02 relative units, respectively; NS) and no differences in Rad protein expression using a specific anti-peptide Rad antibody (1.05 +/- 0.18, 1.14 +/- 0.08, and 1.08 +/- 0.21 units/mg protein, respectively; NS). However, Rad protein levels were positively correlated with BMI (r = 0.43, P = 0.03) and percentage body fat (r = 0.55, P < 0.005), two independent measures of obesity, and negatively correlated with resting metabolic rate (r = 0.49, P = 0.01). In multiple regression analyses, percentage body fat and resting metabolic rate independently accounted for 30 and 10% of individual variability in muscle Rad protein expression. In conclusion, Rad expression in skeletal muscle is not altered as a function of insulin resistance or NIDDM in humans. However, these data, for the first time, implicate a role for Rad in regulating body composition and energy expenditure and provide a framework for studies designed to elucidate Rad's cellular functions.
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PMID:Muscle Rad expression and human metabolism: potential role of the novel Ras-related GTPase in energy expenditure and body composition. 903 1

Alterations of the renal function in the isolated perfused rat kidney system after application of two bacterial RNases, Bacillus intermedius RNase (binase) and ribonuclease produced by Bacillus amyloliquefaciens (barnase), were investigated with two different treatment regimens in comparison with catalytically inactive derivates of the enzymes, photooxidated at the active site His101 binase and inactive mutant His102Gln barnase. For the in vitro approach the test enzymes were dissolved in the perfusion media and applied to the kidney after removal from the animal. Alternatively, the test ribonucleases were administered to rats in vivo and the renal effects were assessed in the isolated perfused rat kidney 1 and 6 h after treatment. In the in vitro regimen both active enzymes induced time- and concentration-dependent nephrotoxicity reflected in enhancement of urinary protein excretion, decline of glucose reabsorption, increase of gamma-glutamyltranspeptidase and alkaline phosphatase activities in urine. In vivo administration of active binase induced functional impairment of the isolated perfused organ in a similar way. None of the inactive RNases in both regimens and at all concentrations tested altered any renal parameter. The results suggest that RNA degradation may be involved in the nephrotoxic effects of bacillar RNases.
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PMID:Nephrotoxic effects of bacterial ribonucleases in the isolated perfused rat kidney. 916 Jan 9

Population spike amplitude was measured in hippocampal slices under conditions of 20-min glucose and oxygen deficit ("in vitro ischemia") with or without ribonuclease A. In control slices the response was gradually decreased within 3 +/- 2 min after the onset of hypoxia/hypoglycemia. This process continued during 13 +/- 6 min of reperfusion. The reperfusion restored the amplitude up to 70 +/- 17% of its initial level within 1.5 h after the onset of this procedure. Addition of ribonuclease delayed the beginning of the response decrease (by 8 +/- 2 min) and increased the level of its restoration (up to 113 +/- 23%) after the reperfusion. It is suggested that ribonuclease prevents from the energy exhaustion by preserving the cellular energy stores.
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PMID:[Ribonuclease improves the function of hippocampal slices in the postischemic period]. 918 15

Alcoholic myopathy occurs in up to two thirds of alcohol misusers and is characterized by selective atrophy of type II (anaerobic, fast-twitch) fibers; type I (aerobic, slow twitch) fibers are relatively unaffected. Both clinical and animal studies have indicated that skeletal muscle RNA content is reduced in response to ethanol exposure, and contributes to impaired protein synthesis. We hypothesized that the reduction in muscle RNA may be due to raised ribonuclease (RNase) activities that enhance RNA catabolism. To test this hypothesis, we measured the total tissue and plasma RNase activities as well as the activities of general (RNase A) and specific or "restriction" RNases (T1L, T2L) in ethanol-treated rats. Chronically treated rats were fed a nutritionally complete liquid diet with 35% of calories as ethanol. Weight-matched controls were pair-fed with isocaloric glucose. Rats were killed at time-points up to 6 weeks. For comparative purposes, the effect of acute (24 hr) starvation was also analyzed in a second group of rats relative to a group of control rats allowed free access to food and water over 24 hr. Results showed that the type II fiber-predominant plantaris muscle exhibited a significant increase in total RNase, RNase A and RNase T1L activities (increases ranged from +59% to +196%; P-values between 0.025 and 0.01) concomitant with large falls in RNA and protein content. In contrast, none of the RNase activities measured in the type I fiber-predominant soleus muscles were significantly affected; compositional changes were also smaller in the soleus. This effect was independent of reduced nutrition. In conclusion, the raised total RNase, RNase A and RNase T1L activities may contribute to the type II fiber-specific reduction in total RNA in chronically ethanol-treated rats. In turn, this may contribute to the alterations in cellular protein metabolism seen under these treatments.
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PMID:Skeletal muscle ribonuclease activities in chronically ethanol-treated rats. 966 Mar 15

The present study investigates the role of metal catalysed oxidation in the formation of Advanced Glycation End products (AGEs). Rat tail tendon collagen was incubated with glucose (250 mM) and increasing concentrations of copper ions (5-500 microM) under physiological conditions of temperature and pH. After 1 and 3 weeks of incubation the level of AGEs in collagen samples were estimated by enzyme linked immunoassay, using antibodies raised against AGE ribonuclease. It was observed that the presence of metal ions significantly increased the rate of accumulation of AGEs. The increase was dependent on the concentration of metal ions present in the incubation medium. Free radical scavengers such as mannitol, benzoate, catalase, and the antiglycating agent aminoguanidine almost completely inhibited the formation of AGEs. Incubation of collagen with copper ions alone did not show any increase in crosslinking, as detected by cyanogen bromide digestion, and AGEs formation. Further it was also noted that glycoxidation, i.e., oxidation of glycated collagen, was the major pathway that leads to increased formation of AGEs. These results indicate that metal-catalyzed oxidation and free radicals play a major role in the formation of AGEs. This work also strongly suggests that increased oxidative stress in diabetes may accelerate the formation of AGEs and thus contribute to the pathogenesis of diabetic complications.
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PMID:The role of metal-catalyzed oxidation in the formation of advanced glycation end products: an in vitro study on collagen. 968 Jan 71

We have investigated the effect of advanced glycation end products (AGEs) on the crosslinking of collagen. The potential pathological significance of AGEs and the altered metabolism of ascorbic acid (ASA) in diabetes have prompted us to investigate the role of ASA in the crosslinking and advanced glycation of collagen. Rat tail tendons were incubated with ASA and dehydroascorbic acid (DHA) under physiological conditions of temperature and pH, and the crosslinking and the level of AGEs were analyzed. Analysis of crosslinking was conducted by pepsin solubility and cyanogen bromide digestion. Level of AGEs was estimated by enzyme-linked immunosorbent assay (ELISA) using antibodies raised against AGE-ribonuclease. It was noted that ASA and DHA induced crosslinking of collagen and stimulated the formation of AGEs. It was also noted that these pathways were dependent on oxidative conditions. Similarly incubation of collagen with AGEs, prepared by the in vitro incubation of bovine serum albumin (BSA) with glucose, also resulted in increased crosslinking. The extent of crosslinking was dependent on the duration of incubation. The novel finding of this study, which is in contrast to the earlier reports on glucose-induced crosslinking of collagen, was that AGEs-induced crosslinking of collagen was not inhibited by radical scavengers and the metal chelator. EDTA, whereas glucose-induced crosslinking of collagen was almost completely prevented by free radical scavengers. The increased fluorescence intensity observed in collagen incubated with AGEs was also not prevented by radical scavengers. Estimation of AGEs by ELISA revealed an increased accumulation of AGEs in collagen incubated with AGE-BSA. The inhibitory effect of aminoguanidine and aspirin on AGEs-induced modification of collagen, strongly suggests that the amino-carbonyl interaction between AGEs and collagen may play a key role in the crosslinking process. The results obtained in this study indicate that soluble AGEs can directly induce crosslinking of collagen and this process is independent of oxidative conditions. From these results it may be hypothesized that glucose, under oxidative conditions, reacts with proteins to form potentially reactive end products called AGEs. These AGEs, once formed, could induce crosslinking of collagen even in the absence of both glucose and oxygen.
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PMID:Advanced glycation end products induce crosslinking of collagen in vitro. 974 85

Living hippocampal slices from Wistar rats were used to study the dynamics of changes in population electrical responses in field CA1 to electrical stimulation of Shaffer collaterals during the development of ischemia (imposed by exclusion of oxygen and glucose from the perfusion solution). These studies showed that during ischemia, addition of ribonuclease (a blocker of protein synthesis) to the perfusion solution resulted in a significantly smaller increase in the latent period of the response and slowed the onset of the reduction in the amplitude of the evoked potential, and promoted faster recovery of the response after the ischemia session ended. It is suggested that the reduction in protein synthesis due to ribonuclease preserved energy reserves in the nerve tissue, which in turn promoted more complete recovery of neuron function in the post-ischemic period.
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PMID:Ribonuclease improves the state of hippocampal sections in the post-ischemic period. 976 5

Oligomers of glucose and oligosaccharides released from glycoproteins were derivatized with 2-aminobenzamide. As this fluorophore imparts no charge to the oligosaccharides, several strategies were investigated to achieve capillary electrophoresis (CE) separation of both neutral and charged derivatized glycans. Micellar electrokinetic capillary chromatography (MEKC) with the addition of anionic surfactants was evaluated as a first approach: sodium dodecyl sulfate (SDS) produced the best separation of the oligoglucose fragments, where the migration was inversely related to their degree of polymerization. To demonstrate the applicability of this method for complex carbohydrate analysis, oligosaccharide mixtures derived from ribonuclease B (RNase B) and alpha-acid glycoprotein (alpha-AGP) were analyzed. A satisfactory separation for the high-mannose structures found in RNase B could be obtained, whereas charged oligosaccharides from alpha-AGP were poorly resolved. Cyclodextrin-modified CE was chosen as the second approach: the effect of the addition of sulfobutylether-beta-cyclodextrin (SBE-beta-CD) or sulfobutylether-gamma-cyclodextrin (SBE-gamma-CD) on the electrophoretic mobilities and resolution of neutral and charged oligosaccharides was then studied. Selectivity of sialylated structures could be further improved by using anionic cyclodextrins (CDs) instead of micelles. However, this latter approach failed to baseline-resolve the different high-mannose structures of RNase B. A successful separation of the complex mixture of oligosaccharides from alphaalpha-AGP was obtained with the addition of 4% of SBE-gamma-CD and triethylamine (TEA) in a phosphate buffer, pH 6.7.
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PMID:Investigation of micelles and anionic cyclodextrins as pseudostationary phases for the capillary electrophoresis separation of oligosaccharides derivatized with 2-amino-benzamide. 984 71


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