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:3.1.4.1 (phosphodiesterase)
18,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Calcitonin gene-related peptide (CGRP) is widely distributed in sensory neurons and nerve fibers. To clarify the function of CGRP on the immune system, the effect of CGRP on phagocytosis by peritoneal macrophages was examined by means of flow cytofluorometry. CGRP enhanced phagocytosis of latex beads in a dose-dependent manner. Because the phosphodiesterase inhibitor 3-isobutyl, 1-methylxanthine (IBMX) enhanced the CGRP-induced enhancement of phagocytosis, the enhancement might be mediated by cAMP. In the presence of mannan, the phagocytosis was suppressed and the CGRP-induced enhancement was also blocked, suggesting that mannose receptors on macrophages were involved in mediating the phagocytosis of latex beads, and CGRP enhanced the mannose receptor-mediated phagocytosis. The present results indicate that CGRP can modulate the function of macrophages in nerve terminals of sensory neurons during the development and maintenance of inflammation.
...
PMID:Enhancement of phagocytosis by calcitonin gene-related peptide (CGRP) in cultured mouse peritoneal macrophages. 897 38

Because of the importance of oligodendrocytes (OL) in forming and maintaining myelin in the CNS and the fact that the remyelination in the CNS is very limited in contrast to the peripheral nervous system, we investigated the effect of a chemically defined medium OLDEM, previously characterized by the maintenance of mature myelinating OL, on oligodendroblasts (or OL progenitors) in culture. The effect of each component of this medium as well as different combinations of them were also examined. Cultures were examined at different developmental stages immunocytochemically for developmental markers, such as transferrin, sulfatides, myelin basic protein and proteolipid protein. OLDEM accelerated the appearance of developmental markers and concomitant morphological changes. Furthermore, myelin-specific enzymes such as glycerophosphorylcholine phosphodiesterase; p-nitro-phenolphosphocholine phosphodiesterase; 2'3'-cyclic nucleotide 3'-phosphodiesterase and UDP galactose: ceramide galactosyltransferase had enzymatic activities similar to values found in pure myelin, indicating that OLDEM allows the optimal expression of myelin-related genes. The effect of each OLDEM constituent was evaluated by immunocytochemistry and by measurement of enzymatic activities. With each single additive or multiple combinations, oligodendrocytes displayed different degrees of maturation. Deletion of selenium, glucose, and galactose severely affected cell survival as well as enzymes expression in young cultures. However, older cultures were more resistant to these deletions. Putrescine and insulin did not cause such effects on survival, but their absence affected cell maturation. None of the OLDEM additives individually supported survival and/or maturation. Enzyme assays performed on isolated myelin-like membranes or the cells soma revealed a redistribution of the activity between these fractions as the cell matured. The biological role of each of these constituents on the maturation of the oligodendroglial cells is discussed. These observations indicate that OLDEM constituents have a powerful effect on OL progenitor maturation, and membrane formation. This medium will be used for investigating the remyelination potential of adult OL progenitors.
...
PMID:Acceleration of the maturation of oligodendroblasts into oligodendrocytes and enhancement of their myelinogenic properties by a chemically defined medium. 921 75

Injury of endothelial cells (EC) has been postulated as the initial trigger of the progression of atherosclerosis in patients with diabetes mellitus. We previously reported that decrease in a novel endothelium-specific growth factor, hepatocyte growth factor (HGF), by high D-glucose might be a trigger of endothelial injury. However, the physiological role of the local vascular HGF system has not yet been clarified. To investigate the role of HGF in endothelial injury, we initially examined the effects of HGF on endothelial injury induced by serum deprivation. Decrease in EC number by serum deprivation was significantly attenuated by addition of HGF as well as recombinant basic fibroblast growth factor, whereas vascular endothelial growth factor showed no effect. Apoptotic changes in EC induced by serum deprivation were also significantly attenuated by addition of HGF (p < 0.01). Given the protective action of HGF, we next studied the physiological role of local HGF production in endothelial regulation. We focused on the protective actions of prostaglandin (PG) I2, PGE and a phosphodiesterase type 3 inhibitor (cilostazol) on endothelial injury by high glucose, since these agents are widely used in the treatment of peripheral arterial disease which is frequently observed in diabetic patients. Treatment of human aortic EC with PGE1, PGE2, and a PGI2 analogue (beraprost sodium) as well as cilostazol stimulated EC growth. HGF concentration in conditioned medium from EC treated with PGE1, PGE2 or PGI2 analogue as well as cilostazol was significantly higher than that with vehicle (p < 0.01). Interestingly, treatment with PGI2 analogue or cilostazol attenuated high D-glucose-induced EC death, which was abolished by neutralizing anti-HGF antibody. Moreover, decreased local HGF production by high D-glucose was also significantly attenuated by PGI2 analogue or cilostazol. Finally, we tested the effects of PGE, PGI2 analogue and cilostazol on local HGF production in human aortic vascular smooth muscle cells (VSMC). Although high D-glucose treatment resulted in a significant increase in VSMC number, PGI2 analogue and/or cilostazol treatment had no effects on VSMC growth. However, the decrease in local HGF production by high D-glucose was significantly attenuated by addition of PGI2 analogue or cilostazol. Overall, this study demonstrated that treatment with PGE, PGI2 analogue or cilostazol prevented aortic EC death induced by high D-glucose, probably through the activation of local HGF production. Increased local vascular HGF production by prostaglandins and cilostazol may prevent endothelial injury, potentially resulting in the improvement of peripheral arterial disease.
...
PMID:Role of hepatocyte growth factor in endothelial regulation: prevention of high D-glucose-induced endothelial cell death by prostaglandins and phosphodiesterase type 3 inhibitor. 930 Feb 42

Gustin, a zinc-metalloprotein constituting about 3% of human parotid saliva protein was previously isolated and characterized as a single polypeptide chain of 37kDa with one mole of zinc tightly bound to the protein. It exhibited biological activity activating calmodulin dependent bovine brain cAMP phosphodiesterase and was decreased in saliva of patients with loss of taste in whom taste buds showed a specific pathological morphology. Determination of its primary structure by amino acid sequence revealed it was identical with carbonic anhydrase (CA) [EC 4.2.1.1] VI and had two N-linked glycosylation sites. Analysis by reverse phase HPLC and SDS-PAGE before and after deglycosylation confirmed a single peak with molecular weight of the purified protein being 37kDa, the deglycosylated protein, 33kDa. N-linked carbohydrate chains contained N-acetyl glucosamine, galactose, mannose, and fucose interior to di, tri and tetra sialyated termini. By isoelectric focusing five increasingly acidic pI values were determined consistent with addition of sialic acid as the terminal carbohydrate residue on the N-linked glycoforms of the protein. Gustin was found to exhibit CA activity but was inhibited by known CA inhibitors in a different manner than CA I or II. These findings, consistent with analysis of previous investigators, indicate that parotid saliva gustin is CA VI.
...
PMID:Gustin from human parotid saliva is carbonic anhydrase VI. 978 98

Sildenafil, a selective inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5), is a well-tolerated and highly effective treatment for erectile dysfunction. The mechanism of action of sildenafil depends on activation of the nitric oxide (NO)-cGMP pathway during sexual stimulation, which results in corpus cavernosal smooth muscle relaxation and penile erection. Endogenously derived NO is also involved in blood pressure regulation through its effect on basal vascular tone, which is mediated by cGMP levels. Organic nitrates and NO donors exert their therapeutic effects on blood pressure and vascular smooth muscle by the same mechanism as endogenous NO. Since both sildenafil and organic nitrates exert their pharmacologic effects via increases in cGMP concentrations, a double-blind, placebo-controlled, crossover study was undertaken to investigate the effects of sildenafil coadministered with glyceryl trinitrate on blood pressure and heart rate in healthy male subjects. The hemodynamic effects of sildenafil were also evaluated in a second placebo-controlled crossover study in men with hypertension who were taking the calcium antagonist amlodipine, which has a mechanism of action that does not involve the cGMP pathway. In the first crossover study, subjects were treated with oral sildenafil (25 mg, 3 times a day for 4 days) or placebo and then challenged on day 4 with a 40-minute, stepwise, intravenous infusion of glyceryl trinitrate (0.5 mg/mL in 5% dextrose at an initial infusion rate of 2.5 microg/min and doubling every 5 minutes to a maximum rate of 40 microg/min) 1 hour after taking sildenafil or placebo. On day 5, subjects received a sublingual glyceryl trinitrate tablet (500 microg) 1 hour after taking 25 mg of sildenafil or placebo. During sildenafil treatment, the subjects were significantly less tolerant of intravenously administered glyceryl trinitrate than during placebo treatment, based on the occurrence of a >25 mm Hg decrease in blood pressure or the incidence of symptomatic hypotension (p <0.01). When a sublingual glyceryl trinitrate tablet was administered on day 5, a 4-fold greater decrease in systolic blood pressure was observed for the subjects during the sildenafil treatment period than during the placebo treatment period. The changes in heart rate were negligible during both glyceryl trinitrate challenges. In conclusion, sildenafil potentiated the hypotensive effects of glyceryl trinitrate, an organic nitrate. Thus, sildenafil administration to patients who are using organic nitrates, either regularly and/or intermittently, in any form is contraindicated. In the second crossover study, men with hypertension, who were taking 5 or 10 mg/day of amlodipine, received a single oral dose of 100 mg sildenafil or placebo. Coadministration of sildenafil did not significantly affect the pharmacokinetics of amlodipine. In the 4 hours after dosing, differences in the mean maximum change from baseline in supine systolic and diastolic blood pressures between the sildenafil plus amlodipine and the placebo plus amlodipine treatment periods were -8 mm Hg and -7 mm Hg, respectively (p < or =0.002). The mean maximum supine heart rate increased 2.1 beats/min during sildenafil plus amlodipine treatment and decreased 1.5 beats/min during placebo plus amlodipine treatment (p <0.02). The adverse events in this study were predominantly mild or moderate and did not cause discontinuation of treatment. Adverse events considered to be related to sildenafil treatment included headache, nausea, and dyspepsia. In patients with hypertension who were taking amlodipine therapy, sildenafil produced additive, but not synergistic, reductions in blood pressure. The difference in the mean maximum change from baseline in blood pressure between sildenafil plus amlodipine and placebo plus amlodipine was comparable to the decrease in blood pressure reported for healthy men taking sildenafil alone. (ABSTRACT TRUNCATED)
...
PMID:Sildenafil citrate and blood-pressure-lowering drugs: results of drug interaction studies with an organic nitrate and a calcium antagonist. 1007 39

Tropical grain legumes represent potentially important feed for farm animals. However, diarrhoea and poor growth performance have been reported, due to the various anti-nutritional factors they contain. This study addressed in particular whether dietary cowpea impaired the growth of pigs, whether the small intestinal Na+/D-glucose coabsorptive transport capacity was decreased, whether the Cl- secretory capacity was increased, and, finally, whether these parameters were affected by heat treatment of cowpea. Pigs, 4 weeks old, were fed for 3 weeks with one of three diets: (i) standard soy, (ii) 75% of soy substituted with raw cowpea, or (iii) 75% of soy substituted with heat-treated cowpea. The absorptive and secretory capacities of the jejunum and ileum were measured with the Ussing chamber technique. Weight gain, feed intake, pancreatic protein and enzyme concentrations and levels of the blood hormones glucagon and cholecystokinin were also measured. The Na+ transport capacity was measured as the increase in short-circuit current (Isc) when D-glucose was added to the luminal side in the Ussing chambers. Isc was significantly higher in the jejunum from raw cowpea-fed pigs than in the jejunum from standard soy-fed pigs, with no difference between the two cowpea-fed groups. The phosphodiesterase inhibitor theophylline was subsequently added bilaterally, and the increase in Isc indicated the cAMP-depedent Cl- secretory capacity. In the jejunum this was significantly higher in raw and heat-treated cowpea-fed pigs than in standard soy-fed pigs. In contrast, there were no differences in the ileal transport capacities. There were no differences in the pancreatic protein and trypsin concentrations or the blood hormones, but the raw cowpea-fed pigs had significantly lower pancreatic amylase than standard soy-fed pigs. Weight gain and feed intake were lowest in the cowpea-fed groups, with no significant difference between the two groups. In conclusion, the hypothesis of impaired small intestinal absorption of D-glucose and Na+ as causing malabsorption, and therefore impaired growth, during cowpea substitution in the feed may be firmly rejected. The increased Cl- secretory capacity, although moderate, may contribute to the higher incidence of post-weaning diarrhoea in cowpea-fed pigs, as observed in other studies. Additionally, the decreased food intake, feed conversion and weight gain were unaffected by heat treatment, further suggesting involvement of heat-stable anti-nutritional factors.
...
PMID:Effects of dietary substitution with raw and heat-treated cowpea (Vigna unguiculata) on intestinal transport and pancreatic enzymes in the pig. 1063 95

A novel N-glycosylated, mannose-rich protein has been purified approx. 4000-fold from human liver in a seven-step procedure including ion-exchange chromatography and fractionation on concanavalin A-Sepharose, Sephadex G-75 and oligo(dT)-cellulose matrices. The molecular mass of the protein is 46 kDa when measured by gel filtration (i.e. under non-denaturing conditions) and 60 kDa by SDS/PAGE (i.e. under denaturing conditions). The protein possesses two DNA backbone-incising activities, namely, the random introduction of single-strand breaks in native DNA and the rupture of the phosphodiester linkage internal to cyclobutyl pyrimidine dimers, the major class of DNA lesions induced by solar UV rays. Both activities are optimal at pH 5.0 in vitro, although the non-specific nuclease displays appreciable activity at neutral pH, depending on the buffer composition. The protein has been named acidic nuclease/intra-cyclobutyl-pyrimidine-dimer-DNA phosphodiesterase (AN/IDP). As a nuclease, the protein 'prefers' a linear DNA structure over a covalently closed circular molecule and is more proficient at digesting single-stranded than double-stranded DNA. The polynucleotide cleavage products of the nuclease contain 5'-OH and 3'-PO(4) termini, which are refractory to direct rejoining by DNA ligases. Depending on the substrate, the nuclease activity exhibits a temperature optimum of 50 degrees C or greater, and is neither stimulated by Mg(2+) or Ca(2+) nor inhibited by Zn(2+). AN/IDP is present in human liver and in cultured human cells of both fibroblastic and lymphocytic origins. Intracellularly, the protein can be readily detected in both the cytosolic and nuclear fractions, although much more (approx. 3-fold) is found in the latter fraction. We propose that this bifunctional enzyme may be involved in both apoptotic DNA digestion and metabolism of cyclobutyl pyrimidine dimers in UV-irradiated human cells.
...
PMID:Purification and characterization of a novel human acidic nuclease/intra-cyclobutyl-pyrimidine-dimer-DNA phosphodiesterase. 1064 17

The ability of acute insulin treatment to elicit a redistribution of the liver insulin-like growth factor-II/ mannose 6-phosphate (IGF-II/M6P) receptor has been studied in rats, using cell fractionation. Injection of insulin (0.4-50 microg) led to a time- and dose-dependent decrease in IGF-II binding activity in Golgi-endosomal (GE) fractions, along with an increase in activity in the plasma membrane (PM) fraction; only receptor number was affected. Quantitative subfractionation of the microsomal fraction on sucrose density gradients showed that IGF-II binding activity distributed similarly to galactosyltransferase (a Golgi marker), at slightly higher densities than in vivo internalized (125)I-insulin, and at lower densities than 5' nucleotidase and alkaline phosphodiesterase (two plasma membrane markers). Insulin treatment led to a slight time-dependent and reversible shift of IGF-II binding activity toward higher densities. Subfractionation of the GE fraction on Percoll gradients showed that IGF-II binding activity was broadly distributed, with about 60% at low densities coinciding with galactosyltransferase and early internalized (125)I-insulin and with 40% at high densities in the region of late internalized (125)I-insulin. Insulin treatment caused a time-dependent and reversible shift of the distribution of IGF-II binding activity toward low densities. On SDS-PAGE, the size of the affinity-labeled IGF-II/M6P receptor was comparable in GE and PM fractions (about 255 kDa), but on Western blots receptor size was slightly lower in the latter (245 kDa) than in the former (255 kDa). Insulin treatment did not affect the size, but modified the abundance of the IGF-II/M6P receptor in a manner similar to that of IGF-II binding. In vivo chloroquine treatment fully suppressed the changes in IGF-II binding activity in liver GE and PM fractions observed in insulin-treated rats. We conclude that insulin elicits a time-dependent and reversible redistribution of liver IGF-II receptors from Golgi elements and endosomes to the plasma membrane, presumably via early endosomes.
...
PMID:Insulin-induced redistribution of the insulin-like growth factor II/mannose 6-phosphate receptor in intact rat liver. 1072 96

N-linked oligosaccharide chains released by hydrazinolysis from yellow lupin seed diphosphonucleotide phosphatase/phosphodiesterase were fluorescence labeled and separated by high performance liquid chromatography (GlycoSep N and GlycoSep H columns). Exoglycosidase sequencing elucidated the structures of 24 separated N-glycans. Thirty percent of isolated glycans were found to be of high-mannose type (three to eight mannosyl residues), 42% were complex type and 26% belonged to paucimannosidic type. Among complex type glycans, structures with Lewis(a) epitope were identified. It is very unusual to find all types of plant N-glycans in one protein. Possible reasons for such a broad spectrum of N-glycan structures are discussed.
...
PMID:Structural analysis of N-glycans from yellow lupin (Lupinus luteus) seed diphosphonucleotide phosphatase/phosphodiesterase. 1104 90

N-Acylethanolamines including anandamide (an endogenous ligand for cannabinoid receptors) are released from N-acylphosphatidylethanolamine (N-acyl-PE) by the catalysis of a phosphodiesterase of the phospholipase D type. The enzyme was solubilized from the particulate fractions of rat heart with the aid of octyl glucoside, and partially purified by anion-exchange chromatography. The enzyme hydrolyzed N-palmitoyl-PE with a specific activity of 17 nmol/min/mg protein at 37 degrees C. The enzyme activity increased dramatically up to 30-fold by millimolar order of Ca(2+). Ca(2+) could be replaced with other divalent cations such as Co(2+), Mg(2+), Mn(2+), Ba(2+), Sr(2+) and Ni(2+). The hydrolysis of N-arachidonoyl-PE (a precursor of anandamide) was also markedly stimulated by Ca(2+).
...
PMID:Marked activation of the N-acylphosphatidylethanolamine-hydrolyzing phosphodiesterase by divalent cations. 1142 Jan 81


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---