Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.1.5 (neuropathy target esterase)
 1,070 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of this study was to investigate in the rat heart and liver the effects of an acute administration of three anthracyclines, doxorubicin, epirubicin and pirarubicin, and an anthracenedione, mitoxantrone, on the membrane peroxidative status, which was estimated by the composition of polyunsaturated fatty acids (PUFA), and on the activities of the enzymes involved in membrane repair processes and lipid hydroperoxide detoxification. Rats were injected for four consecutive days with the drugs or saline (control) and killed 24 hr after the last injection. All the drugs induced an increase in plasma thiobarbituric reactive substances and alpha-tocopherol concentrations, both expressed per milligram of plasma lipids. Plasma vitamin A was decreased by about a factor of two by all the drugs. The fatty acid profile in the heart lipids showed that the polyunsaturated species (20:4 n-6, 22:6 n-3) remained at the same or even higher levels after anthracycline treatment. This can be explained by the fact that the activities of the enzymes involved in either the recycling of membrane phospholipids, such as phospholipases A1 and A2 (EC 3.1.1.4 and EC 3.1.1.32), lysophospholipases (EC 3.1.1.5) and acylCoA:lysophosphatidylcholine acyltransferases (EC 2.3.1.23), or hydroperoxide detoxification, such as selenium-dependent glutathione peroxidase (GSH-PX, EC 1.11.1.9) and glutathione S-transferases (GSH-T, EC 2.1.5.18), were maintained at the same level of activity after the antitumoral treatment. In liver, membrane phospholipid levels of PUFA were maintained as well as the activities of phospholipid-metabolizing enzymes. GSH-PX activity was not affected whereas that of GSH-T was slightly lowered by the drugs. These results suggest that during acute antitumoral-induced lipid peroxidation of membranes, the multi-enzymatic complex of the immediate processes of repair and detoxification is fully operational, allowing the membrane to rapidly recover its functional status. The results are discussed in the context of the equivocal relationships between antitumoral-induced lipid peroxidation and cardiac disturbances.
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PMID:Heart and liver membrane phospholipid homeostasis during acute administration of various antitumoral drugs to the rat. 141 37

The developmental profiles of the protective mechanisms of heart against peroxidative injury during neonatal growth was examined in the pigs of three different age groups. Lipid peroxidation expressed in terms of malonaldehyde formation was considerably higher in the pig hearts of the 8-10 day age group compared to that either by newborn or adult age groups. The four principal antioxidative enzymes, superoxide dismutase, glutathione peroxidase, glutathione reductase, and glucose-6-phosphate dehydrogenase (G6PD), were enhanced during early neonatal growth and, with the exception of G6PD, all other enzymes were further enhanced during further growth to adulthood. G6PD activity dropped significantly in adult heart. The phospholipid contents of myocardial membrane between newborn and week-old pigs did not vary significantly. Total phospholipids and phosphatidylcholine contents were significantly higher in adult heart compared to those in neonatal heart. The enzymes of phospholipid synthesis and degradation, fatty acyl CoA synthetase (FACS), phospholipase A2 (PLA2), lysophospholipase (LPL), and lysophophatidylcholine acyltransferase (LPCAT) increased during early neonatal growth. During further growth to adulthood, FACS decreased, PLA2 did not change, whereas both LPL and LPCAT increased significantly. Analysis of free fatty acids showed that palmitic and stearic acids decreased during the first week of growth, but increased during further growth to adulthood. Oleic acid did not change with aging, but arachidonic acid dropped in adult heart compared to that in neonatal heart. Linoleic, palmitoleic and free fatty acids increased dramatically during the first week of neonatal growth, but dropped thereafter. These results suggest that the unusual peroxidative status of the week-old pig heart is related to the presence of high concentrations of polyunsaturated fatty acids in the membrane phospholipids and not with the antioxidative defense system.
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PMID:Developmental profiles of protective mechanisms of heart against peroxidative injury. 359 80

The purpose of this study was to investigate in rats the effects of three anthracyclines, pirarubicin, doxorubicin and epirubicin on gastric prostaglandin E2 (PGE2) metabolism and phospholipase A2 (PLA2, EC 3.1.1.4) activity. The level of the membrane precursor, arachidonic acid, and the stability of the membrane were investigated by analysis of the composition of fatty acids. Enzymatic activities involved in the turnover of membrane phospholipids such as lysophospholipase (LPase, EC 3.1.1.5) and acyl-CoA lysophosphatidylcholine: acyltransferase (ACLAT, EC 2.3.1.23), and in the detoxification of lipid hydroperoxides, selenium-dependent glutathione-peroxidase (GSH-PX, EC 1.11.1.9) were measured after injection of the drugs for 4 consecutive days. Pirarubicin does not give rise to any changes in these activities but doxorubicin and epirubicin decreased PGE2 production and the activities of PLA2, LPase and ACLAT. GSH-PX activity was not changed by any of the drugs. The decrease in PLA2 activity does not seem to be related to variations in membrane lipid composition because the total phospholipids content was unchanged. The P/S (polyunsaturated/saturated) ratio increased in the doxorubicin group and decreased in the epirubicin group, and the unsaturation index was moderately modified. Arachidonic acid was increased only in the doxorubicin group. In vitro, PLA2 activity was not inhibited by the three drugs in the micromolar range. A marked inhibition was observed at 2.5 mM for pirarubicin and at 1.0 mM for doxorubicin and epirubicin. The Lineweaver-Burk representation showed that these inhibitions were of an uncompetitive type. Pirarubicin may therefore be considered to be an anthracycline without marked side-effects on gastric mucosa. However, the in vitro inhibition of PLA2 activity by anthracyclines does not fully explain the in vitro decrease in PLA2 specific activity observed after doxorubicin and epirubicin treatment, and in this context membrane structure modifications unconnected with the lipid composition can not be excluded. In vivo these phenomena may affect PGE2 synthesis, whose level was lower in the doxorubicin and epirubicin groups than in control group.
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PMID:Effect of anthracyclines on phospholipase A2 activity and prostaglandin E2 production in rat gastric mucosa. 834 60

An animal (rat) model of chronic stress (corticosterone in the drinking water) was used to study the interaction of stress and the organophosphorus (OP) neurotoxicants chlorpyrifos (60 mg/kg subcutaneously in a single dose) and tri-ortho-tolyl phosphate (TOTP, at 75, 150, or 300 mg/kg given 7 times orally in a 2-wk period). Adult male Long-Evans rats were provided with corticosterone in drinking water (400 microg/ml, w/v) for a total of 28 d, which led to significantly decreased weight and decreased cellularity of the thymus and spleen. Seven days after initiation of corticosterone treatment, half of the rats were given chlorpyrifos, and an additional 7 d later the 2-wk, 7-dose treatment of TOTP was initiated. During the 28-d test period, behavior of rats was evaluated using a functional observational battery (FOB), motor activity, and passive avoidance. Reductions in body weight, grip strength, and ambulatory movements occurred as a result of corticosterone treatment. Decreased body weight and grip strength were also elicited by TOTP, and the interactions of corticosterone and TOTP enhanced the effects on body weight and grip strength. Blood cholinesterase levels were obtained during the 28-d study period and found useful for monitoring OP exposure. At the end of the 28-d testing period, rats were sacrificed and activities of cholinesterase, neurotoxic esterase (neuropathy target esterase), and/or carboxylesterase were evaluated in blood, liver, and/or brain regions (basal forebrain, caudate putamen, cerebral cortex, hippocampus). All these esterases in brain were inhibited in a dose-related manner by TOTP, with some enhancement in rats drinking corticosterone-containing water. In addition, choline acetyltransferase, glial acidic fibrillary protein (GFAP), glutathione peroxidase, and superoxide dismutase were evaluated in one or more of the brain regions already identified. Choline acetyltransferase, glutathione peroxidase, and superoxide dismutase activities were unaffected by treatments. However, GFAP was elevated above control levels in the cerebral cortex of rats by all treatments (corticosterone, chlorpyrifos, TOTP). Neuropathological examination revealed early stages of dose-related increased distal myelinated fiber axonal degeneration seen in the medullary fasciculus gracilis at only the highest dose of TOTP (300 mg/kg).
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PMID:Neurologic and immunologic effects of exposure to corticosterone, chlorpyrifos, and multiple doses of tri-ortho-tolyl phosphate over a 28-day period in rats. 1471 79

Individual variations studies are important to understand the snakebite envenoming and to improve the antivenom production and its effectiveness. In this way, the objective of this study was a comparative analysis of intraspecific variation in the venom composition of 22 Crotalus durissus collilineatus specimens through proteomic techniques. Venoms were fractionated by RP-FPLC, and analyzed by SDS-PAGE and mass spectrometry. Although similar, chromatographic and electrophoretic profiles showed significant qualitative and quantitative differences. Some venom components were identified for the very first time in C. d. collilineatus, such as glutathione peroxidase, nerve growth factor, 5'-nucleotidase, angiotensin-converting enzyme, carboxypeptidase, phosphodiesterase, glutaminyl cyclase and phospholipase B. Regarding hyaluronidase activity, 2 venoms did not present detectable enzyme activity in the tested amounts. Additionally, in vivo crotalic envenoming in mice showed that venoms from different specimens resulted in diversified changes of biochemical and immunological parameters, such as creatine kinase and interleukin 6. This study demonstrated significant intraspecific variations in the venom of C. d. collilineatus, which may impact the production and effectiveness of the antivenom therapy. BIOLOGICAL SIGNIFICANCE: This study performed the proteomic and functional analyzes of 22 C. d. collilineatus individual venoms and verified the occurrence of quali and quantitative variations among them. The venoms evaluated caused envenomings with different changes in biochemical and immunological parameters. These results confirm the need to use a pool of venoms with the greatest possible variability in the preparation of antivenoms, in order to improve their effectiveness. In addition, this study was able to identify for the first time 8 different proteins in this subspecies venom, increasing knowledge about its composition and showing that it is a source of these proteins with possible biotechnological applications.
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PMID:Global proteomic and functional analysis of Crotalus durissus collilineatus individual venom variation and its impact on envenoming. 2946 64