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)

The in vitro metabolism of [14C]toluene by liver microsomes and liver slices from male Fischer F344 rats and human subjects has been compared. Rat liver microsomes produced only benzyl alcohol from toluene. Liver microsomes from human subjects metabolized toluene to benzyl alcohol, benzaldehyde, and benzoic acid. Liver microsomes from one human donor also produced p-cresol and o-cresol. The overall rate of toluene metabolism by human liver microsomes was 9-fold greater than by rat liver microsomes. Human liver microsomal metabolism of benzyl alcohol to benzaldehyde required NADPH and was inhibited by carbon monoxide and high pH (pH 10). but was not inhibited by ADP-ribose or sodium azide. These results suggest that cytochrome P-450, rather than alcohol dehydrogenase, was responsible for the metabolism of benzyl alcohol to benzaldehyde. Human and rat liver slices metabolized toluene to hippuric acid and benzoic acid. The overall rate of toluene metabolism by human liver slices was 1.3-fold greater than by rat liver slices. Cresols and cresol conjugates were not detected in human or rat liver slice incubations. Covalent binding of [14C]toluene to human liver microsomes and slices was 21-fold and 4-fold greater than to the comparable rat liver preparations. Covalent binding did not occur in the absence of NADPH, was significantly decreased by coincubation with cysteine, glutathione, or superoxide dismutase, and was unaffected by coincubation with lysine. Protease and ribonuclease digestion decreased the amount of toluene covalently bound to human liver microsomes by 78% and 27% respectively. Acid washing of human liver microsomes had no effect on covalent binding.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Metabolism and covalent binding of [14C]toluene by human and rat liver microsomal fractions and liver slices. 198 39

A method for the modification of enzymes by MPEG carrying an amino acid or peptide as a spacer arm is described and tested with aliphatic or aromatic side chains amino acids. The procedure involves MPEG activation by p-nitrophenylchloroformate for the amino acid or peptide coupling that is in turn activated for the protein binding. The advantage of the method resides in the possibility to introduce proper reporter groups between the polymer and the protein as norleucine for a direct evaluation of the bound polymer chains, tryptophan for structural studies of the polymer-protein adduct, and radioactive amino acid for pharmacokinetic investigations. The method was positively tested with arginase, ribonuclease, and superoxide dismutase as enzymes of therapeutic value.
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PMID:Enzyme modification by MPEG with an amino acid or peptide as spacer arms. 202 78

Metallothioneins that bind copper and zinc have an Mr of 6500 daltons, consist of a single polypeptide chain of 61 amino acids, 25-30 percent of whose residues are cysteine, have a metal-binding capacity of between 5 and 7 g atoms/mol, and contain no disulfide bonds or aromatic amino acids. Zincthionein has been postulated to participate in the transport and storage of zinc, which is involved in more than 235 metalloenzymes, including thymidine kinase, RNA polymerase, and ribonuclease, which in turn play crucial roles in the replication and transcription of DNA during cell division. In addition, trace elements including zinc modulate immune response and function. Conversely, zinc deficiency state causes, for example, thymic atrophy and lymphopenia and modifies antibody-mediated responses to both T-cell-dependent and T-cell-independent antigens. The concentrations of copper, zinc, and metallothionein and the copper/zinc ratio are modified in a number of malignancies. For example, the levels of metallothionein in normal and in malignant human livers are 471 and 75 micrograms/g, respectively. In addition, the copper/zinc ratio is significantly increased in human pancreatic cancer from 1.40 to 2.70. Furthermore, studies involving 64Cu in tumor-bearing mice showed that the distribution of 64Cu was altered and that all tumors contained a relatively high level of 64Cu. Moreover, the activity of superoxide dismutase to remove free oxygen radicals is lower in malignant tissues. Finally, the results of clinical studies suggest that the monitoring of the serum copper/zinc ratio may be a valuable tool, not only in determining the extent of malignancies, but also in predicting the efficacy of treatments.
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PMID:The status of zinc, copper, and metallothionein in cancer patients. 328 43

Studies in animal models suggest that oxygen radicals are important in the pathogenesis of acute pancreatitis. Cerulein, a decapeptide isolated from the skin of the frog, Hyla caerula, is closely related to the C-terminus of cholecystokinin and it is a potent stimulant of pancreatic exocrine secretion. The aim of the present study was to measure the activity of endogenous scavengers, superoxide dismutase, catalase and glutathione levels in cerulein-induced acute pancreatitis in rats. We found that the plasma amylase and ribonuclease levels in the pancreatitis group were both significantly high (p < 0.01, p < 0.05, respectively) when compared with the control group. Although superoxide dismutase and glutathione levels of pancreatic tissue were decreased significantly (p < 0.01, p < 0.01 respectively), we observed a significant increase (p < 0.01) in catalase activity in the cerulein treated group compared to the control group. Therefore, we concluded that the profound alteration of the activities of endogenous scavengers (superoxide dismutase, catalase) and glutathione depletion occurring after cerulein-induced pancreatitis seemed to be important in tissue injury and may provide the basis for successful therapy of the disease.
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PMID:The endogenous scavengers in cerulein-induced acute pancreatitis. 754 30

The plasma-lymphatic distribution of ribonuclease (RNase), superoxide dismutase (SODase), and catalase (CTase) modified by monomethoxy (polyethylene glycol) (mPEG) was studied in rats. The lymphatic bioavailability (FL) of individual enzymes administered intravenously was determined on the basis of plasmatic and lymphatic concentration curves. It was concluded that FL values depend on enzyme-adduct molecular weight (m.w.). The highest FL value was found in mPEG-RNase (the lowest m.w.), medium value in mPEG-SODase (intermediate m.w.), and the lowest one in mPEG-CTase (the highest m.w.). The binding of these enzymes in the lymphatic tissue of iliac, intestinal, brachial and neck nodes was also proportional to their molecular weight. The lymphatic binding was dependent on the node localization, higher concentrations being found in the iliac and neck nodes in contrast to the other nodes (intestinal, brachial).
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PMID:Distribution of catalase, ribonuclease and superoxide dismutase modified by monomethoxy (polyethylene glycol) into rat central lymph and lymphatic nodes. 886 65

A major limitation to the use of rat hepatocytes in the study of drug metabolism and toxicity is the rapid loss of CYPs. We demonstrate that the culture of rat hepatocytes results in a rapid loss of liver-specific CYP2C11 mRNA and transcripts encoding the general housekeeping gene copper-zinc superoxide dismutase (CuZnSOD) as well as poly(A(+)) mRNA. These losses are accelerated by fibronectin, which has no effect on the transcription of CYP2C11 and CuZnSOD. However, fibronectin, an extracellular matrix protein involved in cell adhesion and spreading, induces ribonuclease (RNase) activity. Fibronectin also increases hepatocyte diameter and data are presented that cell spreading is involved in the loss of both CYP2C11 and CuZnSOD mRNAs. The use of functional blocking antibodies demonstrates that fibronectin is operating through its alpha(5)beta(1) integrin receptor and genistein, a tyrosine kinase inhibitor, prevents hepatocyte spreading, RNase induction, and CYP2C11 mRNA loss. Collectively, the data indicate that hepatocytes in vitro actively promote the extinction of their phenotype via the autocrine effects of fibronectin rather than the current consensus that they simply lose differentiated function, such as CYP2C11 expression, through the absence of extracellular matrix proteins. The substrate specificity of the ribonuclease induced is also considered.
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PMID:Fibronectin-mediated hepatocyte shape change reprograms cytochrome P450 2C11 gene expression via an integrin-signaled induction of ribonuclease activity. 1104 44

Snake envenomation employs three well integrated strategies: prey immobilization via hypotension, prey immobilization via paralysis, and prey digestion. Purines (adenosine, guanosine and inosine) evidently play a central role in the envenomation strategies of most advanced snakes. Purines constitute the perfect multifunctional toxins, participating simultaneously in all three envenomation strategies. Because they are endogenous regulatory compounds in all vertebrates, it is impossible for any prey organism to develop resistance to them. Purine generation from endogenous precursors in the prey explains the presence of many hitherto unexplained enzyme activities in snake venoms: 5'-nucleotidase, endonucleases (including ribonuclease), phosphodiesterase, ATPase, ADPase, phosphomonoesterase, and NADase. Phospholipases A(2), cytotoxins, myotoxins, and heparinase also participate in purine liberation, in addition to their better known functions. Adenosine contributes to prey immobilization by activation of neuronal adenosine A(1) receptors, suppressing acetylcholine release from motor neurons and excitatory neurotransmitters from central sites. It also exacerbates venom-induced hypotension by activating A(2) receptors in the vasculature. Adenosine and inosine both activate mast cell A(3) receptors, liberating vasoactive substances and increasing vascular permeability. Guanosine probably contributes to hypotension, by augmenting vascular endothelial cGMP levels via an unknown mechanism. Novel functions are suggested for toxins that act upon blood coagulation factors, including nitric oxide production, using the prey's carboxypeptidases. Leucine aminopeptidase may link venom hemorrhagic metalloproteases and endogenous chymotrypsin-like proteases with venom L-amino acid oxidase (LAO), accelerating the latter. The primary function of LAO is probably to promote prey hypotension by activating soluble guanylate cyclase in the presence of superoxide dismutase. LAO's apoptotic activity, too slow to be relevant to prey capture, is undoubtedly secondary and probably serves principally a digestive function. It is concluded that the principal function of L-type Ca(2+) channel antagonists and muscarinic toxins, in Dendroaspis venoms, and acetylcholinesterase in other elapid venoms, is to promote hypotension. Venom dipeptidyl peptidase IV-like enzymes probably also contribute to hypotension by destroying vasoconstrictive peptides such as Peptide YY, neuropeptide Y and substance P. Purines apparently bind to other toxins which then serve as molecular chaperones to deposit the bound purines at specific subsets of purine receptors. The assignment of pharmacological activities such as transient neurotransmitter suppression, histamine release and antinociception, to a variety of proteinaceous toxins, is probably erroneous. Such effects are probably due instead to purines bound to these toxins, and/or to free venom purines.
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PMID:Ophidian envenomation strategies and the role of purines. 1173 31

Familial amyotrophic lateral sclerosis (FALS) is often caused by gain-of-function mutations in Cu,Zn-superoxide dismutase (SOD1). Multiprobe ribonuclease protection assays (RPAs) were used to investigate expression of 36 different cytokines and apoptosis-related genes in spinal cords of mice that ubiquitously express human SOD1 bearing a glycine (r) alanine substitution at residue 93 (G93A-SOD1). Mice were studied at late presymptomatic stage (80 days), and at 120 days when the animals experience severe hindlimb paralysis and accumulation of oxidatively modified proteins. Spinal cord tissue from G93A-SOD1 mice expressed a selective subset of macrophage-typical cytokines (monokines) including interleukin (IL)1alpha, IL1beta and IL1RA at 80 days increasing by 120 days. Contrastingly, T-cell derived cytokines (lymphokines) including IL2, IL3 and IL4 were detected at low levels in non-transgenic mice but these were not elevated in G93A-SOD1 mice even at 120 days. Apoptosis-related genes were generally unaffected at 80 days but multiple caspases and death receptor components were up-regulated at 120 days; the only exceptions being FADD and the tumor necrosis factor (TNF)alpha receptor p55 which was up-regulated at 80 days and increased further at 120 days. These data indicate that in the G93A-SOD1 mouse: (i) cytokine expression changes precede bulk protein oxidation and apoptosis gene expression; (ii) lymphocyte contributions to cytokine expression in FALS are likely minor; and (iii) TNFalpha and its receptors may link inflammation to apoptosis in ALS.
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PMID:Temporal patterns of cytokine and apoptosis-related gene expression in spinal cords of the G93A-SOD1 mouse model of amyotrophic lateral sclerosis. 1212 37

The dipolar relaxation process induced by the excitation of the single tryptophan residue of four proteins (staphylococcal nuclease, ribonuclease-T1, phosphofructokinase, and superoxide dismutase) has been studied by dynamic fluorescence measurements. A new algorithm taking into account the relaxation effect has been applied to the fluorescence decay function obtained by phase-shift and demodulation data. This approach only requires that fluorescence be collected through the whole emission spectrum, avoiding the time-consuming determination of the data at different emission wavelengths, as usual with time-resolved emission spectroscopy. The results nicely match those reported in the literature for staphylococcal nuclease and ribonuclease-T1, demonstrating the validity of the model. Furthermore, this new methodology provides an alternative explanation for the complex decay of phosphofructokinase and human superoxide dismutase suggesting the presence of a relaxation process even in proteins that lack a lifetime-dependent spectral shift. These findings may have important implications on the analysis of small-scale protein dynamics, since dielectric relaxation directly probes a local structural change around the excited state of tryptophan.
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PMID:The recovery of dipolar relaxation times from fluorescence decays as a tool to probe local dynamics in single tryptophan proteins. 1294 Dec 97

In order to compare transcription profiles in cultivars of Malus domestica that are differentially sensitive to apple scab (Venturia inaequalis), two cDNA libraries were constructed using the suppression subtractive hybridization (SSH) method. Subtraction hybridization was performed between cDNAs from uninfected young leaves of the resistant cultivar Remo and the susceptible Elstar. In total, 480 EST clones were obtained: 218 (ELSTAR) clones represent transcripts that are preferentially expressed in Elstar, while the other 262 (REMO) are derived from RNAs that are more highly expressed in Remo. The putative functions of about 50% of the cloned sequences could be identified by sequencing and subsequent homology searches in databases or by dot-blot hybridization to known targets. In the resistant cv. Remo the levels of transcripts encoding a number of proteins related to plant defense (such as beta-1,3-glucanase, ribonuclease-like PR10, cysteine protease inhibitor, endochitinase, ferrochelatase, and ADP-ribosylation factor) or detoxification of reactive oxygen species (such as superoxide dismutase) were highly up-regulated relative to the amounts present in cv. Elstar. Most surprising was the large number of clones derived from mRNAs for metallothioneins of type 3 (91 out of 262) found in the REMO population. The corresponding transcripts were only present in small amounts in young uninfected leaves of the cv. Elstar, but were up-regulated in the susceptible cultivar after inoculation with V. inaequalis. These results indicate that constitutively high-level expression of PR proteins may protect cv. Remo from infection by different plant pathogens.
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PMID:Characterization by suppression subtractive hybridization of transcripts that are differentially expressed in leaves of apple scab-resistant and susceptible cultivars of Malus domestica. 1581 49


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