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:3.1.3.1 (alkaline phosphatase)
47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Incubation of pig kidney microvillar membranes with Bacillus thuringiensis or Staphylococcus aureus phosphatidylinositol-specific phospholipase C (PI-PLC) resulted in the release of a number of glycosyl-phosphatidylinositol (GPI)-anchored hydrolases, including alkaline phosphatase (EC 3.1.3.1), amino-peptidase P (EC 3.4.11.9), membrane dipeptidase (EC 3.4.13.19), 5'-nucleotidase (EC 3.1.3.5) and trehalase (EC 3.2.1.28). Of these five ectoenzymes only for membrane dipeptidase was there a significant (approx. 100%) increase in enzymic activity upon release from the membrane. Maximal activation occurred at a PI-PLC concentration 10-fold less than that required for maximal release. In contrast solubilization of the membranes with n-octyl beta-D-glucopyranoside had no effect on the enzymic activity of membrane dipeptidase. A competitive e.l.i.s.a. with a polyclonal antiserum to membrane dipeptidase indicated that the increase in enzymic activity was not due to an increase in the amount of membrane dipeptidase protein. Although PI-PLC cleaved the GPI anchor of the affinity-purified amphipathic form of pig membrane dipeptidase there was no concurrent increase in enzymic activity. In the absence of PI-PLC, membrane dipeptidase in the microvillar membranes hydrolysed Gly-D-Phe with a Km of 0.77 mM and a Vmax. of 602 nmol/min per mg of protein. However, in the presence of a concentration of PI-PLC which caused maximal release from the membrane and maximal activation of membrane dipeptidase the Km was decreased to 0.07 mM while the Vmax. remained essentially unchanged at 624 nmol/min per mg of protein. Overall these results suggest that cleavage by PI-PLC of the GPI anchor on membrane dipeptidase may relax conformational constraints on the active site of the enzyme which exist when it is anchored in the lipid bilayer, thus resulting in an increase in the affinity of the active site for substrate.
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PMID:Activation of the glycosyl-phosphatidylinositol-anchored membrane dipeptidase upon release from pig kidney membranes by phospholipase C. 798 Apr 26

The present investigation evaluated the changes in bronchoalveolar lavage fluid (BALF) biochemical constituents and indices of bronchoalveolar lavage cell functions to detect early lung injury in rats following intraperitoneal administration of cyclophosphamide (CP). Rats were exposed to a single intraperitoneal injection of CP (200 or 300 mg/kg body weight). Experimental and control rats were sacrificed at various time intervals (2, 3, 5, 7, 11, 21, and 42 days after cessation of exposure), and lung lavage was performed to examine several markers of lung injury. Biochemical analyses revealed dose-related increases in BALF angiotensin converting enzyme activity, total protein, lactate, lactate dehydrogenase, and N-acetyl-beta-D-glucosaminidase (NAG) levels on days 2, 3, 5, 7, and dose-related increases in albumin, alkaline phosphatase, acid phosphatase, and lipid peroxidation on days 2, 3, 5, 7, and 11 after CP treatment. In contrast, reduced levels of ascorbic acid and glutathione (GSH) content were observed in lung lavage fluid. We also examined bronchoalveolar lavage cells for acid hydrolases (acid phosphatase, beta-glucuronidase, NAG) and GSH content. Activity of acid hydrolases was slightly elevated on day 2 and peaked on days 3, 5, and 7. However, lavage cell GSH content was decreased. Thus, measurements of pulmonary changes by analyzing lavage fluid and lavage cell functions seems to be a useful marker for assessing the early onset and development of CP-induced lung injury.
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PMID:Cyclophosphamide induced early biochemical changes in lung lavage fluid and alterations in lavage cell function. 820 29

Phorbol-myristate acetate (PMA) is commonly used to produce experimental edema and other tissue injuries in the lung. Lung injuries induced by the administration of PMA has been shown to be mediated mainly by neutrophils. Neutrophils recruited to the lower respiratory tract may damage lung tissues by releasing reactive oxygen species, neutral proteases, and lysosomal enzymes. The present study was conducted to investigate whether alpha-tocopherol, entrapped in dipalmitoylphosphatidylcholine liposomes and delivered directly to the lung, could counteract some of the PMA-induced lung injuries. Plain liposomes or alpha-tocopherol containing liposomes (8 mg alpha-tocopherol/kg body weight) were intratracheally instilled into the lungs of rats 24 hr prior to PMA exposure (25 micrograms/kg) and treated rats were killed 3 hr later. Lungs of control animals exposed to PMA developed an increase in lung weight and lipid peroxidation as well as a decrease in lung angiotensin converting enzyme (ACE) and alkaline phosphatase (AKP) activities. PMA treatment also caused an increase in myeloperoxidase (MPO) activity in the lung, suggestive of neutrophil infiltration. Pretreatment of PMA-treated rats with plain liposomes had no effect on PMA-induced injuries. In contrast, pretreatment of rats with liposomal alpha-tocopherol, 24 hr prior to PMA administration, resulted in a significant elevation of pulmonary alpha-tocopherol concentration, accompanied by a concomitant reduction in MPO activity and reversal of PMA-induced changes in lung edema, lipid peroxidation, ACE and AKP activities. These results appear to demonstrate that the intratracheal administration of a liposome-associated lipophilic antioxidant, such as alpha-tocopherol, can significantly ameliorate the toxic effects of reactive oxygen species, putatively released from PMA-stimulated pulmonary target cells and infiltrating neutrophils.
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PMID:Prevention of phorbol myristate acetate-induced acute lung injury by alpha-tocopherol liposomes. 870 53

Paraquat is a broad-spectrum herbicide known to produce lung injury via oxidative stress-mediated mechanisms. Different pharmacological strategies have been explored to reduce the formation of these reactive oxygen species and/or prevent their toxic effects in the treatment of paraquat poisoning. The present study was carried out to investigate whether the antioxidant alpha-tocopherol, incorporated into liposomes and delivered directly to the lungs of rats, could protect the organ against the long-term toxic effects of paraquat. Plain liposomes (composed of dipalmitoylphosphatidylcholine, DPPC) or alpha-tocopherol liposomes (8 mg alpha-tocopherol/kg body weight) were administered intratracheally to animals 24 h prior to an intraperitoneal injection of paraquat dichloride (20 mg/kg) and rats were killed 0, 1, 4, 6, 8, 10, 12, 16, 19 or 24 days after paraquat treatment. Results of this study showed that lungs of animals treated with paraquat were extensively damaged, as evidenced by significant increases in lung weight and decreases in lung angiotensin converting enzyme (ACE) and alkaline phosphatase enzyme (AKP) activities. Moreover, paraquat treatment: resulted in a significant reduction in the number of neutrophils in the blood of rats with a concurrent increase in the pulmonary myeloperoxidase activity, suggestive of neutrophil infiltration in the lungs of treated animals. Pretreatment of rats with liposomes alone did not significantly alter the paraquat-induced changes of all parameters examined. On the other hand, pretreatment of rats with alpha-tocopherol liposomes, 24 h prior to paraquat challenge, attenuated paraquat-induced changes in ACE, AKP and myeloperoxidase activities but failed to prevent increases in lung weight. Thus, pretreatment of rats with liposome-associated alpha-tocopherol appears to protect the lung against some of the toxic effects of paraquat.
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PMID:Intratracheally administered liposomal alpha-tocopherol protects the lung against long-term toxic effects of paraquat. 871 70

1. Morphine-6-glucuronide is one of the major metabolites of morphine. The potent analgesic action of this compound together with its potential lower apparent toxicity in man, when compared with morphine, indicated its clinical importance. 2. Primary cultures of porcine brain capillary endothelial cells were used to study brain penetration of morphine-6-glucuronide. Biochemical characterization of the cell cultures revealed a marked enrichment in enzymatic activity of alkaline phosphatase (56 fold) and angiotensin converting enzyme (230 fold) as compared to whole brain tissue. By immunostaining the presence of vimentin, factor VIII, the tight junction associated protein ZO-1, and P-glycoprotein was shown. Functional characterization revealed that the carrier system responsible for transport of neutral amino acids was intact. 3. Uptake and transport of morphine-6-glucuronide was marginal and in the range of the extracellular marker sucrose. However, uptake of morphine-6-glucuronide was enhanced significantly (P < 0.0001) in presence of the inhibitors of P-glycoprotein, verapamil or vincristine. The finding that morphine-6-glucuronide may serve as a substrate for P-glycoprotein was confirmed in multidrug-resistant P388 tumour cells. 4. We conclude that penetration of the blood-brain barrier by morphine-6-glucuronide may depend on the expression of the product of the multidrug-resistance (MDR) gene in brain capillary endothelial cells.
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PMID:Evidence for P-glycoprotein-modulated penetration of morphine-6-glucuronide into brain capillary endothelium. 886 18

Utilization of primary cultured brain capillary endothelial cells (BCECs) as an in vitro model of the blood-brain barrier (BBB) depends on the extent to which cultured BCECs retain the in vivo characteristics. Recently, we have reported that consistent isolation of BCECs that mimic the in vivo BBB depends on whether a specific ratio between the weight of the isolation enzyme (collagenase/dispase) and the weight of the capillaries present during the isolation is used. Since it is possible for the same weight of an enzyme to possess different activity levels, it is felt that activity rather than weight of an enzyme should be used in arriving at the above ratio. Therefore, using bovine brain as the source of BCECs, we have quantified the amount of collagenase/dispase needed for optimal isolation of BCECs and retention of their phenotypic properties in terms of collagenase/dispase activity per g of capillaries. Monolayers of bovine BCECs isolated at 0.15 or 0.30 units of collagenase and 2.06 or 4.12 units dispase per g of capillaries gave the best overall quality as judged by their permeability characteristics and the activities of angiotensin converting enzyme, alkaline phosphatase and gamma-glutamyl transpeptidase.
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PMID:Biochemical characteristics of a primary blood-brain barrier cell culture system as a function of the activity of the proteases used in tissue disaggregation. 888 12

Reactive oxygen species are known to play a key role in the development of acute lung injury, and such injury can be alleviated by pretreating the lung with a suitable antioxidant preparation. In this study, we evaluated and compared the antioxidant efficacy of two liposomal preparations: liposomes containing only alpha-tocopherol versus bifunctional liposomes containing both alpha-tocopherol and glutathione (GSH). alpha-Tocopherol liposomes (2 mg alpha-tocopherol/animal) or liposomes containing both alpha-tocopherol and GSH (2 mg alpha-tocopherol and 10 mumol GSH/animal) were intratracheally instilled into the lungs of rats 30 min prior to a challenge with paraquat dichloride (30 mg/kg, i.p.); animals were killed 24 hr post-paraquat challenge. Lungs of paraquat-challenged animals were damaged extensively as evidenced by increases in lung weight, indicative of edema, and decreases in lung activities of angiotensin converting enzyme (ACE) and alkaline phosphatase (AKP), indicative of endothelial and alveolar type II epithelial cell injuries, respectively. While the pretreatment of rats with alpha-tocopherol liposomes or liposomes containing both alpha-tocopherol and GSH significantly attenuated paraquat-induced changes in lung ACE activity to more or less the same extent, the bifunctional liposomal preparation conferred additional protection to alveolar type II epithelial cells, as evidenced by a significantly higher pulmonary AKP activity. Our results also showed that both liposomal preparations failed to ameliorate paraquat-induced lung edema despite a significant protection of pulmonary endothelial cells, suggesting that paraquat-induced edema formation may be independent of endothelial cell damage. In conclusion, liposome-associated antioxidants can protect the lung against an oxidant challenge, and the extent of protection appears to be related to the characteristics of each antioxidant formulation.
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PMID:Alleviation of paraquat-induced lung injury by pretreatment with bifunctional liposomes containing alpha-tocopherol and glutathione. 893 65

The present study was carried out to investigate whether the intravenous administration of liposomal alpha-tocopherol can result in a significant localization of the antioxidant in the injured lung. Male Sprague-Dawley rats were injected with paraquat dichloride (20 mg/kg, ip.) and 4, 24 or 48 h later, they were given an intravenous injection of a liposomal alpha-tocopherol preparation (20 mg alpha-tocopherol in 128 mumoles liposomal lipid/kg) labelled with [14C]dipalmitoylphosphatidylcholine (DPPC) and [3H]alpha-tocopherol. Animals were killed and their lungs removed for analysis 24 h after liposomal treatment. To demonstrate whether the extent of uptake of radioactive alpha-tocopherol liposomes was directly related to the extent of residual lung injury, additional groups of animals were also injected with higher doses (30 and 40 mg/kg body weight) of paraquat dichloride and 48 h later, were treated with liposomal alpha-tocopherol; animals were then killed 24 h after liposomal alpha-tocopherol treatment. The intraperitoneal injection of paraquat dichloride resulted in time- and dose-dependent decreases in angiotensin converting enzyme and alkaline phosphatase activities suggesting that the toxicant injures both the capillary endothelial cells and alveolar type II epithelial cells, respectively. The recovery of intravenously administered radioactive alpha-tocopherol in the lungs of saline-treated animals was found to be about 2% of the initial dose 24 h post-liposomal treatment. However, in paraquat-treated animals, there was an increased localization of the labelled alpha-tocopherol to the lung, resulting in a difference of pulmonary delivery by as much as 2-3 fold compared to that in a normal lung. The 3H/14C ratio, representing the recovery of [3H]alpha-tocopherol and [14C]liposomes, was practically constant and there was a linear relationship between the measurable lung injury index and the corresponding recovery of radiolabelled alpha-tocopherol in the lung. Our results appear to suggest that the residual pulmonary injury augments the delivery of liposomal alpha-tocopherol to the lung.
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PMID:The pulmonary uptake of intravenously administered liposomal alpha-tocopherol is augmented in acute lung injury. 895 87

By means of CM-Sephadex C-25, DEAE-Sephadex A-50, Sephadex G-200, and Sephadex G-75 chromatographies, a lupus anticoagulant like protein (LALP) from Agkistrodon halys brevicaudus was purified. On SDS-PAGE, the purified LALP had a molecular weight of 25,500 daltons under non-reducing condition and 15,000 daltons under reducing condition. The isoelectric point was pH 5.6. Its N terminal amino acid sequencing revealed a mixture of 2 sequences: DCP(P/S)(D/G)WSSYEGH(C/R)(Q/K). It was devoid of phospholipase A, fibrino(geno)lytic, 5'-nucleotidase, L-amino acid oxidase, phosphomonoesterase, phosphodiesterase and thrombin-like activities, which were found in crude venom. In the presence of LALP, PT, aPTT, and dRVVT of human plasma were markedly prolonged and its effects were concentration-dependent but time-independent. The inhibitory effect of LALP on the plasma clotting time was enhanced by decreasing phospholipid concentration in TTI test. The individual clotting factor activity was not affected by LALP when higher dilutions of LALP-plasma mixture were used for assay. Russell's viper venom time was shortened when high phospholipid confirmatory reagent was used. Therefore, the protein has lupus anticoagulant property.
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PMID:Purification and characterization of lupus anticoagulant like protein from Agkistrodon halys brevicaudus venom. 897 23

The clinical use of bleomycin in the treatment of squamous cell carcinomas, lymphomas and testicular tumours has been limited by its toxic effects, the most serious being pulmonary injury. The present study was undertaken to investigate whether alpha-tocopherol, incorporated in liposomes and delivered directly to the lung, could offer protection against bleomycin-induced lung damage and fibrosis in the rat. Animals were administered, intratracheally, plain liposomes (composed of dipalmitoylphosphatidylcholine, DPPC) or alpha-tocopherol-containing liposomes (8 mg alpha-tocopherol/kg body weight) and 30 min later, were exposed to bleomycin sulphate (4 units/kg body weight) by intratracheal instillation; treated animals were killed 21 days later. Results of this study showed that lungs of animals treated with bleomycin were seriously damaged, as evidenced by significant histological changes and increases in lung weight, lipid peroxidation, myeloperoxidase activity and hydroxyproline content as well as decreases in lung angiotensin converting enzyme (ACE) and alkaline phosphatase (AKP) activities. Pretreatment of rats with plain liposomes alone did not alter significantly the bleomycin-induced changes of all parameters examined. In contrast, pretreatment of rats with alpha-tocopherol liposomes 30 min prior to bleomycin administration resulted in little or no histological changes and conferred a significant protection against bleomycin-induced changes in edema, lipid peroxidation, hydroxyproline content, and ACE, AKP and myeloperoxidase activities. Results of this study suggested that pretreatment of rats with alpha-tocopherol liposomes can provide a significant protection against bleomycin-induced lung injury.
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PMID:Protective effect of liposomal alpha-tocopherol against bleomycin-induced lung injury. 909 26


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