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

---

Query: EC:3.1.3.5 (5'-nucleotidase)
3,167 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acute 1,2-dichloropropane (DCP) poisoning in humans is relatively frequent in Italy, where DCP is widely diffused as a constituent of commercial solvents and dry cleaners. In this study we have investigated the effects of DCP on intracellular glutathione (GSH) content in main target tissues of male Wistar rats, i.e. liver, kidney and blood, in order to establish if a correlation between DCP-induced GSH depletion and tissue damage exists. Administration of DCP (2 ml/kg body weight orally) caused a dramatic loss of tissue GSH occurring 24 h after DCP intoxication, followed by a slow restoration approaching physiological levels after 96 h. GSH depletion was associated with a marked increase in serum GOT, GPT, 5'-nucleotidase, gamma-glutamyl transpeptidase, alkaline phosphatase, urea and creatinine, and a significant degree of hemolysis. When animals were pretreated with a GSH depleting agent, buthionine-sulfoximine (BSO) (0.5 g/kg body weight) i.p. 4 h before DCP intoxication, an increase of overall mortality was found, significantly different from the group of animals treated with DCP alone. On the contrary, the administration of a GSH precursor, N-acetylcysteine (NAC) i.p. (250 mg/kg body weight) 2 and 16 h after DCCP intoxication prevented the dramatic loss of cellular GSH and reduced the extent of injury in target tissues, as demonstrated by laboratory indices. Furthermore, statistical analysis of the data revealed a correlation between: (1) depletion of liver GSH and increase in serum GOT, GPT, 5'-nucleotidase, (2) depletion of kidney GSH and increase in serum urea and creatinine and (3) depletion of blood GSH and the occurrence of hemolysis.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:1,2-Dichloropropane (DCP) toxicity is correlated with DCP-induced glutathione (GSH) depletion and is modulated by factors affecting intracellular GSH. 198 Apr 7

During the delivery of oxygen by erythrocytes, highly reactive oxygen species such as superoxide anion arise. The presence of reactive species damages the cell constituents. Glutathione (GSH) functions to repair cells when they are attacked by oxidative stress. GSH is synthesized in erythrocytes and glutathione disulfide (GSSG) is transported outside the cells to maintain a high GSH/GSSG ratio. The redox cycle of GSH by glutathione reductase and glutathione peroxidase is closely related to G6PD. Hereditary enzyme deficiency related to GSH metabolism, with hemolytic anemia has been reported. G6PD deficiency causes hemolytic anemia due to insufficiency of the redox cycle of GSH. Deficiency of GSH synthesizing enzymes or glutathione reductase also causes hemolysis. Pyrimidine 5'-nucleotidase deficiency causes hemolytic anemia even when there is a high concentration of GSH. Accumulation of nucleotides in red cells causes inhibition of G6PD activity.
...
PMID:[Impaired glutathione metabolism in hemolytic anemia]. 219 89

(Na+,K+)ATPase activity of rat liver plasma membranes was evaluated in female rats feeding an ethanol containing diet for 46 days (total ethanol ingested, 59.7 g/100 g body wt). Determinations were performed at the end of ethanol treatment or at various times after stopping treatment. (Na+,K+)ATPase and 5'-nucleotidase activities exhibited a 8- and 1.4-fold decrease, respectively, at the end of ethanol ingestion. In contrast no modifications of Mg2+-ATPase activity were observed. There also occurred, in ethanol-treated rats, release of sorbitol dehydrogenase into the blood, fat accumulation in liver cells, and decrease in reduced glutathione (GSH) liver content. A decrease in (Na+,K+)ATPase activity was also found in plasma membranes isolated from hepatocyte suspensions after a 2-hr incubation with 50 mM ethanol or 1 mM acetaldehyde (ACA), in conditions that caused a great fall in hepatocyte GSH content but did not cause cell death. After the cessation of ethanol administration, there occurred a progressive recovery of (Na+,K+)ATPase activity, GSH and triacylglycerol content, and release of sorbitol dehydrogenase. These parameters reached control values 12 hr after ethanol withdrawal. S-Adenosyl-L-methionine (SAM), L-methionine, and N-acetylcysteine (NAC), given to rats during ethanol treatment, prevented the decrease in (Na+,K+)ATPase activity and GSH content. They also reduced steatosis and liver necrosis. The efficiency of these compounds decreased in this order: SAM, methionine, NAC. SAM accelerated the recovery of all parameters studied after ethanol withdrawal, and also protected (Na+,K+)ATPase activity and GSH content of isolated hepatocytes from the deleterious effect of ethanol. These SAM effects were prevented by 1-chloro-2,4-dinitro-benzene, a compound which depletes cell GSH. Treatment of isolated hepatocytes with [35S]SAM led to the synthesis of labeled GSH. The total amount and specific activity of labeled GSH underwent a significant increase, in the presence of 2 mM ethanol or 0.5 mM ACA, which indicates a marked stimulation of GSH synthesis by ethanol and ACA. These data indicate that ethanol intoxication may inhibit (Na+,K+)ATPase activity; an effect that does not seem to depend on cell necrosis. SAM, methionine, and NAC exert various degrees of protection toward ethanol-induced cell injury, which are related to the efficiency of these compounds in maintaining a high GSH pool.
...
PMID:Inhibition by ethanol of rat liver plasma membrane (Na+,K+)ATPase: protective effect of S-adenosyl-L-methionine, L-methionine, and N-acetylcysteine. 253 5

Male Sprague-Dawley rats were treated with clofibrate (CLOF) in the diet for 2 years or with 4 i.p. injections of either diethylnitrosamine (DEN) or benzidine (BZ) followed by phenobarbital (PB) in the diet for 67 weeks, or just with PB for 41 weeks. Animals were killed at frequent intervals, some while still on treatment and others after 3 or 6 months withdrawal of treatment. The livers were subjected to cytochemical measurements of the parenchyma, foci, nodules and carcinomas. The parenchyma of the CLOF groups showed, in general, increases in glucose-6-phosphate dehydrogenase (G-6PD), alpha-glycerophosphate dehydrogenase (alpha-GPD), 5'-nucleotidase (5'-Nu), acid phosphatase (AP) and catalase and decreases in uricase and glutathione (GSH). CLOF induced a low incidence of GSH positive foci; nodules showed universally lower levels of catalase and GSH. In the DEN/PB and BZ/PB groups the parenchyma showed increases (even before PB treatment started) in G-6PD and in gamma-glutamyl transpeptidase (gamma-GT) and decreases in GSH. DEN raised and BZ lowered 5'-Nu. Neither initiator affected alpha-GPD. Both initiators caused a high incidence of foci positive for G-6PD and for gamma-GT; nodules induced by DEN/PB were mainly positive for gamma-GT and showed an erratic response to the other parameters. Carcinomas, found only after DEN/PB, were all positive for G-6PD and, with one exception, all were negative for alpha-GPD, 5'-Nu, AP and GSH. All changes regressed within 3 months of withdrawal of CLOF but not after withdrawal of PB from DEN-initiated animals. In conclusion G-6PD, alpha-GPD and 5'-Nu may be useful histocytochemical parameters for studying the precarcinogenic hepatic changes and nodules induced by peroxisome proliferators and by genotoxic hepatocarcinogens.
...
PMID:A cytochemical study of the livers of rats treated with diethylnitrosamine/phenobarbital, with benzidine/phenobarbital, with phenobarbital, or with clofibrate. 282 19

Erythrocytes from patients with hereditary pyrimidine 5'-nucleotidase (P5N, EC 3.1.3.5) deficiency accumulate large quantities of several pyrimidine nucleotides and their derivatives. In addition, the reduced glutathione (GSH) concentration is elevated in erythrocytes from patients with this enzyme deficiency. In the present study, we were unable to demonstrate any effect of various pyrimidine nucleotides and their derivatives on enzymes of glutathione biosynthesis and metabolism. Thus, elevation of GSH levels in erythrocytes from P5N patients is not a result of modulation of these enzymes by pyrimidine nucleotides and their derivatives.
...
PMID:Pyrimidine nucleotides do not affect the enzymes of glutathione biosynthesis. 286 97

The synergistic hepatotoxicity of dietary disulfiram (DSF) with 1,2-dichloroethane (DCE) subchronically administered by inhalation at three concentration levels (150, 300, and 450 ppm) was studied. The criteria for hepatotoxicity were treatment-related increases in serum activities of sorbitol dehydrogenase, 5'-nucleotidase, and alkaline phosphatase, and in liver-to-body weight ratios. DSF alone did not elicit these responses while DCE at the highest concentration level increased liver-to-body weight ratios and the activity of 5'-nucleotidase. Exposure to DSF alone decreased cytochrome P450 levels, but in combination with DCE, the decrement of cytochrome P450 was additive in a DCE concentration-dependent manner. However, depression of cytochrome P450 by DCE alone was not concentration dependent. Although DSF and DSF/DCE combination increased the activity of glutathione S-transferases (GSTs), both DSF and DCE singly and in combination increased the tissue levels of reduced glutathione (GSH). Evidence is presented showing that the potentiation of the hepatotoxicity of DCE observed in the presence of DSF may be due to an inhibition of microsomal mixed-function oxidase-mediated metabolism of DCE and to a compensatory increase in DCE metabolism to reactive metabolites generated by GST-mediated conjugation of DCE with GSH.
...
PMID:Interaction between 1,2-dichloroethane and tetraethylthiuram disulfide (disulfiram). II. Hepatotoxic manifestations with possible mechanism of action. 378 26

Purified inside-out vesicles from human erythrocytes were used to investigate the active transport of oxidized glutathione (GSSG). Incubation of vesicles and GSSG in the presence of ATP resulted in the transport of GSSG into the vesicles. When vesicles were incubated with reduced glutathione (GSH), no transport was observed. At GSSG concentrations of less than 5 mM, transport was linear up to 4 hr at 37 degrees C. A Lineweaver-Burk plot of the transport rate as a function of GSSG concentration was biphasic and gave apparent Km values of 0.1 and 7.1 mM. The Km for ATP . Mg in this transport process was 0.63 mM at a GSSG concentration of 20 microM and 1.25 mM at a GSSG concentration of 5 mM. The transport rate at low GSSG concentrations was inhibited by CTP or UTP, which acted as competitive inhibitors of ATP; Ki=0.51 mM. This inhibition may account for the high erythrocyte GSH levels observed in pyrimidine-5'-nucleotidase deficiency, a disorder in which erythrocytic levels of CTP and UTP are elevated.
...
PMID:Glutathione transport by inside-out vesicles from human erythrocytes. 693 50

Activities of adenosine deaminase, 5'-nucleotidase, xanthine oxidase, superoxide dismutase, glutathione peroxidase and catalase enzymes were measured in cancerous and non-cancerous adjacent colorectal tissues from 10 patients. Activities of DNA turn-over enzymes (ADA, 5'NT and XO) were found increased and those of free-radical metabolizing enzymes (SOD, GSH-Px and CAT) decreased in cancerous tissues compared with those of non-cancerous adjacent ones. Malondialdehyde (MDA) concentrations in cancerous tissues were also found higher than those of non-cancerous tissues, which indicated accelerated lipid peroxidation in the cancerous tissues. In the correlation analysis, disordered enzymatical relations were observed between the enzymes of both metabolic pathways. Results suggest that activities of purine metabolizing enzymes increase to cope with accelerated purine metabolism in cancerous tissues and, enzymatic antioxidant defense potential of cancerous tissues decreases due to carcinogenic processes in the tissues. Reduced antioxidant defense system makes the cancerous tissue more vulnerable to toxic effects of some free-radical species.
...
PMID:Activities of the enzymes participating in purine and free-radical metabolism in cancerous human colorectal tissues. 992 74

The effect of oxidative stress catalysed by transition metals appears to have a critical relevance for the structure and function not only of membrane lipids but also of integral membrane proteins in a complex lipid-protein assembling, and membrane-dependent function. The integral membrane enzyme 5'-nucleotidase is susceptible to Fe((2+))-ion catalysed oxidative modification, and the extent of enzyme inhibition is in inverse relationship (r = -0.820) with lipid peroxidation (MDA) level. This work is also a comparative study about possible effectiveness of different Fe-ion chelators (deferoxamine, Na-citrate, Na-salicylate, ammonium oxalate and EDTA), antioxidants (GSH, GSH/GSH-Px system, Cu, Zn-SOD and mannitol) and metal cations (Mg(2+) and Mn(2+)) to protect or restore Fe(2+)-ion induced 5'-nucleotidase inhibition and to suppress Fe(2+)-ion enhanced lipid peroxidation. Among the examined chelators it was only deferoxamine and Na-citrate that exerted a fully protective and reactivating ability; among the antioxidants it was only GSH; among the metal cations it was only Mn(2+). The ability to protect or restore 5'-nucleotidase activity and to diminish chain-induced lipid peroxidation is explicable in terms of: metal-binding ability, capacity of taking iron away from a biological molecule, or ability of transferring the damage to itself. After a short incubation period, the iron associated with enzyme or lipid hydroperoxides could be in a labile coordinative linkage, still able to interact with possible ligands or metal cations.
...
PMID:Oxidative modification of rat liver 5'-nucleotidase: the mechanisms for protection and re-activation. 1193 67

The effectiveness of the antioxidant thiol, N-acetylcysteine (NAC), in enhancing methylmercury (CH3HgCl) excretion and its utility as a possible antidote in CH3HgCl poisoning has been reported. NAC, however, has been reported to be ineffective in accelerating excretion of divalent toxic metals, including inorganic mercury, Hg2+. In this study, we evaluated the possible protective effect of short-term pretreatment with NAC against mercuric chloride (HgCl2) toxicity in rat model. This is aimed at determining its chemopreventive or prophylactic benefit in situations of high risk exposure (occupational/industrial) to mercury. Rats were divided into three treatment groups. Group I received saline (10 ml/kg) and served as control. Group II received HgCl2 (5mg/kg) and group III received NAC (10mg/kg) plus (5mg/kg). All administration was via intraperitoneal (i.p.) injection. Saline and NAC were administered for 5days and HgCl2 was administered to rats in groups II and III on the 5th day. Animals were sacrificed 24 hours after HgCl2 injection and samples obtained for biochemical evaluation. Results revealed that single i.p. injection of HgCl2 induced significant renal oxidative damage resulting in significant decrease in the activities of superoxide dismutase (SOD), catalase (CAT), glutathione-s-transferase (GST), depletion of reduced glutathione (GSH) and increase in malondialdehyde (MDA) levels in these rats. The activities of glucose-6-phosphatase (G6Pase) and 5'-nucleotidase (5'-NTD) (markers of microsomal damage) also decreased in these HgCl2 treated rats. The oxidative damage induced by HgCl2 led to significant alterations in renal histology and caused functional impairment (indicated by elevated blood urea nitrogen (BUN) and serum creatinine) in these rats. NAC was effective in attenuating the oxidative damage, functional impairments and histopathological changes that characterized HgCl2 intoxication in this study. Renal antioxidant defense system was re-enforced by NAC, leading to increase in the activities of SOD, CAT, GST and decreases in GSH depletion and MDA level. Our results therefore reveal the ameliorative effect of NAC pretreatment against HgCl2 toxicity in vivo, thus, suggesting its usefulness as a possible chemoprophylactic agent during occupational or industrial exposure to inorganic mercury.
...
PMID:N-acetylcysteine pretreatment ameliorates mercuric chloride-induced oxidative renal damage in rats. 2241 58


1 2 Next >>

---