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:3.6.1.3 (ATPase)
65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In continuation of earlier studies on murine neoplastic liver lesions, we characterized by histochemical methods the phenotype of hepatocellular adenomas and carcinomas induced by single injections of diethylnitrosamine (1.25, 2.5, or 5.0 micrograms/g of body weight) in 15-day-old C57BL/6 x male C3H F1 mice. The hepatocellular adenomas were composed predominantly of basophilic cells but stored excessive amounts of fat and glycogen in large portions of the tumors. Irrespective of the carcinogenic dose, the adenomas showed a consistent histochemical pattern. Glycogen synthase and phosphorylase were highly active in the hepatocytes that stored glycogen. In cells poor in, or free of, this polysaccharide, these enzymes were only moderately active or even inactive. In glycogen-storing parts of the adenomas, the activity of adenylate cyclase was reduced compared with normal liver parenchyma, but in fat-storing portions it was elevated. In a few adenomas, uniform increase in adenylate cyclase activity could be encountered. The levels of ATPase, acid phosphatase, and glucose-6-phosphatase were either increased or decreased. Glucose-6-phosphate dehydrogenase and glyceraldehyde-3-phosphate dehydrogenase showed an increased activity in all adenomas compared with preneoplastic foci, which in turn exhibited a higher glucose-6-phosphate dehydrogenase and glyceraldehyde-3-phosphate dehydrogenase activity than the surrounding parenchyma or the liver of untreated controls. The hepatocellular carcinomas showed remarkable histochemical changes compared with adenomas. The levels of fat and glycogen and the activities of glycogen synthase, phosphorylase, and in most cases also that of glucose-6-phosphate dehydrogenase, were reduced significantly. In contrast, adenylate cyclase, glucose-6-phosphatase, glyceraldehyde-3-phosphate dehydrogenase, and also alkaline phosphatase showed a striking elevation in developing carcinomas. Similar, although more pronounced, histochemical changes were seen in the advanced hepatocellular carcinomas. These observations indicated that progression from adenomas to hepatocellular carcinomas was associated with a change in the activity of several enzymes involved in cell membrane function, glycogen metabolism, the oxidative pentose phosphate pathway, and glycolysis.
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PMID:Histochemical profile of mouse hepatocellular adenomas and carcinomas induced by a single dose of diethylnitrosamine. 184 80

Chronic infection of woodchucks with woodchuck hepatitis virus (WHV) was associated with the development of hepatitis, foci of altered hepatocytes and hepatocellular adenomas and carcinomas. The cytomorphological and cytochemical analysis permitted the identification of three different types of focal lesions; namely, glycogen-storage foci, mixed-cell foci and intermediate-cell foci, each showing a characteristic pattern. The cells of the glycogen-storage foci had clear to acidophilic cytoplasm, and were overloaded with glycogen. They showed a marked elevation in the activity of glucose-6-phosphate dehydrogenase (G6PDH) and malate dehydrogenase (MDH), increased activity of succinate dehydrogenase (SDH), glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and glycerol-3-phosphate dehydrogenase (G3PDH), reduction in the activity of glycogen phosphorylase (PHO), glucose-6-phosphatase (G6Pase), adenosine triphosphatase (ATPase) and adenyl cyclase (ADC), and unchanged activity of glycogen synthase (SYN) and gamma-glutamyl transferase (GGT). The mixed-cell foci mainly consisted of basophilic cells poor in glycogen, but were intermingled with cells containing glycogen. These foci were characterized by a marked decrease in activity of PHO, SYN, G6Pase, G6PDH, ATPase and ADC, and increased activity of GGT, SDH, MDH and GAPDH. The intermediate-cell foci consisted of cells with both basophilic and glycogenotic cytoplasmic compartments, and showed a similar enzyme histochemical profile to the mixed-cell foci, with slight differences in the degree of elevation or reduction of some enzymes. The phenotypic similarities and the close spatial relationship between the foci of altered hepatocytes, and the hepatocellular adenomas and carcinomas in WHV-infected woodchucks, suggest that these lesions are preneoplastic. The focal morphological and metabolic aberrations emerging during hepatocarcinogenesis in WHV-infected woodchuck, are in principle similar to those identified in the course of chemical hepatocarcinogenesis in various species. The focal metabolic aberrations apparently represent a general biological response of the liver parenchyma to oncogenic agents and are closely linked to neoplastic transformation of the hepatocytes.
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PMID:Phenotypic patterns of preneoplastic and neoplastic hepatic lesions in woodchucks infected with woodchuck hepatitis virus. 215 41

Calcium functions as an intracellular second messenger, transducing a variety of hormonal, electrical, and mechanical stimuli by activating a wide range of enzymes. There is evidence, ranging from definitive to strongly presumptive in quality, that lithium can alter many calcium-dependent processes. The list of enzyme systems dependent on calcium and altered by lithium includes adenylate cyclase, glycogen synthase, inositol-1-phosphatase, and calcium adenosine triphosphatase (ATPase). Lithium also interferes with calcium regulation of receptor sensitivity, parathyroid hormone release, microtubule structure, and other systems. All of the neural mechanisms that are hypothesized to explain various psychopharmacological treatments of bipolar illness involve functions that are critically controlled by calcium. Moreover, in every instance, a known action of lithium on calcium function could account for lithium's therapeutic or prophylactic results. From these considerations the dual hypotheses emerge that bipolar illnesses arise from disorders in calcium-regulated functions and that lithium acts by reversing or counterbalancing the effects of these calcium dysfunctions.
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PMID:Lithium mechanisms in bipolar illness and altered intracellular calcium functions. 242 87

In a stop-experiment using the hepatocarcinogen N-nitrosomorpholine, as well as glycogenotic and related lesions, hepatocellular foci with a different histochemical pattern were identified. The outstanding features of these hepatic foci, which may progress to hepatocellular adenoma, were increased activities of mitochondrial glycerol-3-phosphate dehydrogenase (mG3PD), glycogen synthase, pyruvate kinase and glucose-6-phosphatase detected by enzyme histochemistry. Since no decrease in activity of any of the enzymes examined were seen in these foci, compared with normal liver, the term enzymatically hyperactive focus (EHF) is proposed for this type of lesion. Only at the stage of overtly nodular growth did these lesions exhibit some of the characteristic changes seen in nodules developing from glycogenotic foci, namely elevated activities of glucose-6-phosphate dehydrogenase, gamma-glutamyl transferase and glutathione-S-transferase P as well as decreased activities of adenosine-triphosphatase, glucose-6-phosphatase and adenylate cyclase. Some of these enzymes have been used widely in morphometric studies as markers for preneoplastic and neoplastic lesions. The inability to detect early EHF may lead to an underestimation of preneoplastic liver lesions in quantitative studies. Although there are apparent differences in the histochemical patterns of glycogen storing foci and early EHF, these differences tend to disappear during progression to overtly neoplastic lesions. In studies comparing the phenotypic alterations in different types of preneoplastic hepatic lesions, the recognition of EHF may contribute to the distinction of obligatory from facultative phenomena during transformation.
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PMID:Unusual histochemical pattern in preneoplastic hepatic foci characterized by hyperactivity of several enzymes. 256 54

Phospholamban, the putative regulatory proteolipid of the Ca2+/Mg2+ ATPase in cardiac sarcoplasmic reticulum, was selectively phosphorylated by a Ca2+/calmodulin (CaM)-dependent protein kinase associated with a cardiac membrane preparation. This kinase also catalyzed the phosphorylation of two exogenous proteins known to be phosphorylated by the multifunctional Ca2+/CaM-dependent protein kinase II (Ca2+/CaM-kinase II), i.e., smooth muscle myosin light chains and glycogen synthase a. The latter protein was phosphorylated at sites previously shown to be phosphorylated by the purified multifunctional Ca2+/CaM-kinase II from liver and brain. The membrane-bound kinase did not phosphorylate phosphorylase b or cardiac myosin light chains, although these proteins were phosphorylated by appropriate, specific calmodulin-dependent protein kinases added exogenously. In addition to phospholamban, several other membrane-associated proteins were phosphorylated in a calmodulin-dependent manner. The principal one exhibited a Mr of approximately 56,000, a value similar to that of the major protein (57,000) in a partially purified preparation of Ca2+/CaM-kinase II from the soluble fraction of canine heart that was autophosphorylated in a calmodulin-dependent manner. These data indicate that the membrane-bound, calmodulin-dependent protein kinase that phosphorylates phospholamban in cardiac membranes is not a specific calmodulin-dependent kinase, but resembles the multifunctional Ca2+/CaM-kinase II. Our data indicate that this kinase may be present in both the particulate and soluble fractions of canine heart.
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PMID:Identification of membrane-bound calcium, calmodulin-dependent protein kinase II in canine heart. 295 8

Changes in the concentration of several metabolites and enzymes related to carbohydrate metabolism were measured during the growth of Saccharomyces cerevisiae on a mineral medium containing glucose as the limiting nutrient. When about 50% of the original glucose was used the exponential phase ended and the culture entered a 'transition' phase before the complete exhaustion of glucose. In this transition phase several metabolic changes occurred. cAMP, that decreased along growth, reached a constant value of about 0.7 nmol/g dry weight. A pronounced drop in fructose-6-phosphate-2-kinase activity and in the concentration of fructose 2,6-bisphosphate and fructose 1,6-bisphosphate was observed accompanied by a less marked decrease in hexose monophosphates. Trehalase activity also dropped and reached a minimal value at the onset of the stationary phase when synthesis of trehalose began. Glycogen concentration and glycogen synthase activity increased sharply during the transition phase. Plasma membrane ATPase began to increase at the middle of the exponential phase and then, coincident with the glucose exhaustion, a 90% decrease in the measurable activity was observed.
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PMID:Changes in the concentration of cAMP, fructose 2,6-bisphosphate and related metabolites and enzymes in Saccharomyces cerevisiae during growth on glucose. 303 16

The postnatal development of mammalian skeletal muscle is associated with an increased capacity for glycogenolysis. In the present study rabbit skeletal muscle underwent a 7-fold increase in glycogen synthase and glycogen phosphorylase activity over the postnatal period of 0--8 weeks. An enriched fraction of sarcolemma was prepared from neonatal and adult muscle to examine the development of the beta-adrenergic receptor-adenylate cyclase system. Adult membranes possessed a 2-fold greater Na+K+(Mg2+)-ATPase activity and a 6--8 fold greater sodium fluoride- and epinephrine-stimulated adenylate cyclase activity. The activation ratio (effector activity/basal activity) increased 2--3 fold for epinephrine and sodium fluoride in adult sarcolemma. The activation by catecholamines conformed to the physiological beta 2 type response with isoproterenol (1.8 . 10(-8) M) > epinephrine (1.1 . 10(-7) M) > norinephrine (3.2 . 10(-6) M). In contrast, binding studies employing (-)-[3H]dihydroalprenolol showed little difference between neonatal and adult membranes with respect to (1) number of binding sites, (2) equilibrium dissociation constant and (3) displacement of (-)-[3H]dihydroalprenolol by catecholamine agonists. Protein and lipid components of the sarcolemma were also modified during development. Neonatal membranes possessed two glycopeptides of Mr 80000 and 86000, whereas in the adult only a single Mr 113000 species was evident. The total lipid phosphorus and phospholipid composition was unchanged during development. The content of linoleic acid increased approx. 3-fold during development in the phosphatidylcholine, phosphatidylethanolamine and phosphatidylserine phospholipids. The cholesterol content of adult membranes was decreased by 29% compared to neonatal membranes.
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PMID:Beta-adrenergic receptor-adenylate cyclase alterations during the postnatal development of skeletal muscle. 625 11

An insulin-sensitive subcellular system was developed from rat adipocytes consisting of plasma membranes and mitochondria. Direct addition of insulin, concanavalin A or anti-insulin receptor antibody to this system resulted in the production of a mediator substance from the plasma membrane that caused dephosphorylation of the alpha subunit of pyruvate dehydrogenase in the mitochondria with concomitant activation of the enzyme. The mediator activated pyruvate dehydrogenase by activating the pyruvate dehydrogenase phosphatase and not by inhibiting the pyruvate dehydrogenase kinase. This was similar to the mechanism by which insulin causes activation of the enzyme in the intact cell. The insulin-sensitive mediator material from the adipocyte plasma membrane was acid-stable with a molecular weight of 1,000 to 1,500. Our laboratory has shown that the mediator that activates pyruvate dehydrogenase was present in intact adipocytes, hepatoma cells, and IM-9 lymphocytes. Insulin altered the amount or activity of the mediator consistent with the effect of the hormone on the cell. Other laboratories have shown similar effects on skeletal muscle and liver. We have shown the mediator to mimic insulin action on the low Km cyclic adenosine monophosphate (AMP) phosphodiesterase and the (calcium++-magnesium++)-adenosine triphosphatase (Ca++-Mg++)-ATPase of adipocyte plasma membranes in addition to pyruvate dehydrogenase. Other laboratories have shown the mediator to activate glycogen synthase. A body of direct and indirect evidence exists that demonstrates that more than one mediator exists. The chemical nature of the mediator is unknown but probably represents a new family of intracellular mediators of hormone action. These mediators may have clinical relevance in postreceptor defects of obesity and type II diabetes (noninsulin-dependent diabetes mellitus).
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PMID:The chemical mediators of insulin action: possible targets for postreceptor defects. 633 85

As demonstrated previously, liver acini draining the blood from intraportally transplanted pancreatic islets in streptozotocin-diabetic rats are altered in various respects. The hepatocytes in these acini store glycogen and/or fat, and they show an increase in proliferation as well as in apoptotic activity. Thus, they are phenotypically similar to carcinogen-induced preneoplastic liver foci (glycogen-storing foci and sometimes also mixed cell foci). By means of catalytic enzyme histochemistry or immunohistochemistry, we investigated the activity of key enzymes of alternative pathways of carbohydrate metabolism and some additional marker enzymes (well known from studies on preneoplastic hepatic foci) in the altered liver acini surrounding the islet isografts. In addition, the expression of glucose transporter proteins 1 and 2 (GLUT-1 and GLUT-2) were investigated immunohistochemically. The activities of hexokinase, pyruvate kinase, glyceraldehyde-3-phosphate dehydrogenase, and glucose-6-phosphate dehydrogenase were increased, whereas the activities of glycogen phosphorylase, adenylate cyclase, glucose-6-phosphatase, and membrane-bound adenosine triphosphatase were decreased in the altered liver acini. The expression of GLUT-2 was also decreased. GLUT-1 and glutathione S-transferase placental form were not expressed, and the activities of glycogen synthase and gamma-glutamyl-transferase remained unchanged. All changes of the enzyme activities were in line with the well known effects of insulin and resembled alterations characteristic of preneoplastic liver foci observed in different models of hepatocarcinogenesis. It remains to be clarified in long-term experiments whether or not these foci represent preneoplastic lesions and may proceed to neoplasia.
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PMID:Altered liver acini induced in diabetic rats by portal vein islet isografts resemble preneoplastic hepatic foci in their enzymic pattern. 864 65

The first biological action of amylin to be described was the inhibition of insulin-stimulated incorporation of radiolabeled glucose into glycogen in the isolated soleus muscle of the rat. This antagonism of insulin action in muscle was non-competitive, occurring with equal potency and efficacy at all insulin concentrations. Amylin inhibited activation of glycogen synthase, partially accounting for the inhibition of radiolabeled glucose incorporation. However, this did not account for a low rate of labeling at higher amylin concentrations, wherein the radioglycogen accumulation was even less than in incubations where insulin was absent. The principal action of amylin accounting for reduction of insulin-stimulated accumulation of glycogen was activation of glycogen phosphorylase via a cyclic AMP-, protein kinase C-dependent signaling pathway to cause glycogenolysis (glycogen breakdown). At physiological concentrations, amylin activated glycogen phosphorylase at its ED50, but because glycogen phosphorylase is present in such high activity, the resulting flux out of glycogen was estimated to be similar to insulin-mediated flux of glucosyl moieties into glycogen. Thus, in the rat, endogenous amylin secreted in response to meals appeared to mobilize carbon from skeletal muscle. Amylin-induced glycogenolysis resulted in intramuscular accumulation of glucose-6-phosphate and release of lactate from tissue beds that included muscle. When muscle glycogen was pre-labeled with tritium in the three position, amylin could be shown to evoke the release of free glucose. This is made possible by glucosyl moieties cleaved at the branch points in glycogen being released as free glucose, rather than being phosphorylated, as occurs with the bulk of the glycogen glucosyls. Free glucose is free to exit cells via facilitated transport, down a concentration gradient that might exist under such circumstances. When measured by a sensitive technique utilizing efflux of labeled glucose, amylin was reported to not affect muscle glucose transport. In most of the above respects, amylin behaved similarly to catecholamines in skeletal muscle. The pharmacology of amylin's effects on muscle glycogen metabolism was consistent with a classic amylin pharmacology in whole animals and in isolated soleus muscle. In one cell line, the pharmacology was CGRPergic. Amylin, like insulin, stimulated Na+/K+ ATPase activity and enhanced muscle contractility in vitro.
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PMID:Effects in skeletal muscle. 1649 48


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