Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.3.9 (glucose-6-phosphatase)
 3,081 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In 28 dogs the distal articular cartilage of the femur was removed and the regenerating articular surface on the 70th postoperative day was studied histochemically for hexokinase, glucose-6-phosphatase, phosphohexose-isomerase, fructose-1, 6-diphosphatase, aldolase, glyceraldehyde-3-phosphate dehydrogenase, lactate dehydrogenase, lactate dehydrogenase isoenzymes, phosphoglucomutase, phosphorylase, glycogen synthetase, UDP--glucose dehydrogenase, and UDP-glucuronic acid-4-epimerase. The articular surface consisted of fibrous tissue and of cartilage islets. The latter contained cells differentiating into cartilage and young chondrocytes. The glycolytic enzymes reacted positively in the regenerative articular surface. Enzyme activities were higher in the cells (particularly the chondroblasts and young chondrocytes) of the cartilage islets than in the connective tissue. In the cells differentiations into cartilage, beside the LDH isoenzymes characteristic of glycolysis, a significant LDH1 and LDH2 activity was observed. At the same site the presence of fructose-1, 6-diphosphatase-activity could be assumed, but there was no glucose-6-phosphatase activity. Glycogen synthesis proceeded in the cells of the cartilage islets and UDP-glucuronic acid-4-epimerase activity was observed in the differentiated cells. UDP-glucose dehydrogenase activity was positive in every section of the articular surface.
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PMID:Studies on cartilage formation. XX. Histochemical investigation of some enzymes of glycogen metabolsim in regenerative articular surfaces. 18 10

Male outbred Sprague-Dawley rats were fed a choline-deficient diet containing 0.10% DL-ethionine (CDE) for 4, 6, 10, 14 or 22 weeks followed by a standard diet for up to 59 weeks. Liver sections were histochemically analyzed for the following parameters: basophilia, glycogen content and the activities of glycogen synthase (SYN), glycogen phosphorylase (PHO), glucose-6-phosphatase (G6PASE), glucose-6-phosphate dehydrogenase (G6PDH), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), glycerin-3-phosphate dehydrogenase (G3PDH), 'malic enzyme' (MDH), alkaline phosphatase (ALKPASE) and gamma-glutamyltranspeptidase (GGT). The stop experiments revealed that many of the oval cells proliferating during the first 4-6 weeks may undergo necrotic changes and disappear with time, whereas cholangiofibroses appearing in animals fed CDE for at least 10 weeks are persistent lesions. The sequence of lesions seen in this study, leading from persistent oval cells through cholangiofibroses to cholangiofibromas, strongly suggests that the oval cells are the precursor cells of cholangiocellular tumors. The proliferating oval cells and the hepatic foci consisting of clear and acidophilic or mixed cell populations were always spatially separated and no transitions between oval and parenchymal cells were observed. These results argue against a precursor-product relationship between oval and parenchymal cells. Both proliferating and persistent oval cells, cholangiofibroses and cholangiofibromas showed a strong staining for G6PDH, GAPDH, G3PDH, MDH, ALKPASE and GGT; low PHO, SYN and G6PASE activities were also detected in these lesions. Persistent glycogen-storage foci, which developed in all rats fed CDE for 4-14 weeks followed by a normal lab chow for over a year, had increased PHO, G6PDH, MDH, ALKPASE and GGT activities, while SYN, GAPDH and G3PDH activities remained unaltered and G6PASE activity decreased. Mixed cell foci appearing in animals fed CDE for 22 weeks followed by a normal lab chow for 59 weeks had strongly increased G6PDH, GAPDH, G3PDH, MDH, ALKPASE and GGT activities as well as decreased G6PASE activity. These results indicate that the characteristic metabolic pattern of preneoplastic hepatic foci is independent of the further administration of the carcinogenic diet. The shift from glycogen metabolism to glycolysis and the pentose phosphate pathway occurring during the later stages of CDE-induced hepatocarcinogenesis is an autogenous process apparently directing the disturbed carbohydrate metabolism towards alternative metabolic pathways. A similar metabolic shift also seems to take place during cholangiocarcinogenesis.
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PMID:Persistence of the cholangiocellular and hepatocellular lesions observed in rats fed a choline-deficient/DL-ethionine-supplemented diet. 131 Sep 7

Renal clear cell tubules and clear/acidophilic cell tumors were induced in male Sprague-Dawley rats by 7 weeks oral administration (stop model) of N-nitrosomorpholine (NNM) at a concentration of 12 mg/100 ml in the drinking water. Twelve, 23 and 34 weeks after withdrawal of NNM serial cryostat sections of the kidneys were histochemically analyzed for the following parameters: glucose transporter proteins (GLUT1, GLUT2), glycogen content and the activities of glycogen synthase (SYN), glycogen phosphorylase (PHO), glucose-6-phosphatase (G6Pase), glucose-6-phosphate dehydrogenase (G6PDH), hexokinase (HK), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), pyruvate kinase (PK), succinate dehydrogenase (SDH), malate dehydrogenase (MDH), alkaline phosphatase (ALP), acid phosphatase (ACP) and gamma-glutamyltransferase (GGT). Clear cell (glycogenotic) tubules first appeared at 23 weeks, and clear/acidophilic cell tumors at 34 weeks after withdrawal of the carcinogen. G6Pase, ALP, GGT and GLUT2 were absent in clear cell tubules, clear/acidophilic cell tubules, and clear/acidophilic cell tumors indicating a sequential origin of all these types of lesions from the collecting duct system, in line with previous morphological findings. In comparison to the collecting duct epithelium, glycogenotic tubules demonstrated an increased activity of PHO and reduced activities of glycolytic and mitochondrial enzymes, which were accompanied by a strongly reduced expression of GLUT1. Moderately increased activities of glycolytic and mitochondrial enzymes were observed in the clear cells of clear/acidophilic cell tubules and tumors compared with those in glycogenotic tubules. They had slightly increased activities of the glycolytic enzymes GAPDH and PK compared with normal collecting duct epithelium, while most of them were nearly lacking in GLUT1. Our findings suggest that glycogen storage is not due to an increased uptake of glucose from the blood, but results from a disturbance in intracellular flux of metabolites. The development of clear cell tubules from the normal collecting duct epithelium is accompanied by a markedly decreased expression of GLUT1 along with a reduction in glycolytic and mitochondrial enzymes. This reduction of enzyme activities is replaced by an increase in enzyme activities in clear/acidophilic cell tumors indicating a fundamental shift in carbohydrate metabolism during progression from preneoplastic to neoplastic lesions.
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PMID:Sequential changes in glycogen content, expression of glucose transporters and enzymic patterns during development of clear/acidophilic cell tumors in rat kidney. 147 41

Male outbred Sprague-Dawley rats were fed a choline-deficient diet containing 0.10% DL-ethionine for up to 30 weeks. Liver slices from rats killed 4, 6, 10, 14, 22 and 30 weeks after starting the treatment were histochemically analyzed for the following parameters: basophilia, expression of cytokeratin 19 (which in the liver is bile duct epithelial cell-specific), glycogen content and activities of glycogen synthetase (SYN), glycogen phosphorylase (PHO), glucose-6-phosphatase (G6PASE), glucose-6-phosphate dehydrogenase (G6PDH), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), glycerin-3-phosphate dehydrogenase (G3PDH), 'malic enzyme' (MDH), alkaline phosphatase (ALKPASE) and gamma-glutamyltranspeptidase (GGT). The diet induced necrosis of single parenchymal cells and a massive proliferation of oval cells within 4-6 weeks; thereafter cholangiofibroses, cystic cholangiomas and some cholangiofibromas, but no cholangiocarcinomas, were observed. Oval cells, cholangiofibroses, cystic cholangiomas and cholangiofibromas expressed cytokeratin 19, whereas parenchymal cells, foci of altered hepatocytes and hepatocellular adenomas did not; this observation does not support a precursor-product relationship between oval and parenchymal cells. SYN, PHO, G6PASE, G6PDH, GAPDH, G3PDH, MDH, ALKPASE and GGT activities were detected in oval cells; cholangiofibrotic lesions, cystic cholangiomas and cholangiofibromas stained strongly for GAPDH, G3PDH and MDH. In livers from rats fed the diet for 10 weeks, single hepatocytes storing high amounts of glycogen appeared in the parenchyma. There was no indication of a transition from the oval cell population to hepatocytes storing glycogen in excess. Foci of glycogen-storing cells were scattered all over the lobes after 14 and 22 weeks; they had increased G6PASE, G6PDH, ALKPASE and GGT activities. Mixed cell foci and hepatocellular adenomas developed within 22-30 weeks and exhibited a remarkable decrease of G6PASE activity, a strong increase of G6PDH, GAPDH, G3PDH and MDH activities as well as extremely high ALKPASE and GGT activities. The data support the concept that during hepatocarcinogenesis, a number of sequential changes in the activities of various enzymes involved in carbohydrate metabolism occur and that a correlation between morphology and enzyme pattern in the focal lesions does in fact exist. Furthermore, our results suggest that two different cell lineages are involved in the development of cholangiocellular tumors from oval cells and hepatocellular tumors from hepatocytes.
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PMID:Enzyme histochemical and immunohistochemical characterization of oval and parenchymal cells proliferating in livers of rats fed a choline-deficient/DL-ethionine-supplemented diet. 170 20

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

Male Wistar rats were given a single i.v. injection of lead nitrate (10 mumol/100 g body wt) and were killed with matched controls 24, 48, 72 h and 20 days after the treatment. Changes of liver carbohydrate metabolism were studied histochemically testing the following parameters: glycogen content, activities of glycogen synthase (SYN), glycogen phosphorylase (PHO), glucose-6-phosphatase (G6PASE), glucose-6-phosphate dehydrogenase (G6PDH), 6-phosphogluconate dehydrogenase (6PGDH), glyceraldehyde-3-phosphate dehydrogenase (GAPDH). In addition, gammaglutamyltransferase (GGT) activity was demonstrated. Between 24 and 48 h after lead nitrate injection there was a nearly complete loss of liver glycogen. Seventy-two hours later the polysaccharide reappeared in single hepatocytes and after 20 days the livers of the lead-treated animals not only had replenished their glycogen stores but contained even more glycogen than the matched controls. SYN and PHO activities were diminished from 24 to 72 h, but returned to control values after 20 days. G6PASE and GGT remained elevated up to 72 h before dropping to normal at 20 days after treatment. The pentose phosphate pathway enzymes G6PDH and 6PGDH showed the most remarkable changes in livers treated with lead nitrate. G6PDH was already elevated at 24 h, but only in Kupffer cells. At 48 and 72 h, when hepatocytes exhibited a highly increased mitotic rate, the levels of G6PDH, 6PGDH and GAPDH were elevated. After 20 days dehydrogenase activities were comparable to those of controls. The results of this study suggest that a single dose of lead nitrate not only stimulates proliferation of hepatocytes but also induces considerable changes in rat liver carbohydrate metabolism, especially between 24 and 72 h after administration. During that period glycogen metabolism undergoes a strong reduction, whereas gluconeogenesis and particularly the pentose phosphate pathway respond with a remarkable increase. This metabolic profile is most likely associated with lead biotransformation as well as with liver cell proliferation. It corresponds only partially to that found in preneoplastic and neoplastic liver lesions observed in chemical carcinogenesis, and is reversible, in contrast to the persistent alterations associated with neoplastic transformation.
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PMID:Effect of lead nitrate on liver carbohydrate enzymes and glycogen content in the rat. 217 37

Focal hepatocellular lesions, induced in our infant mouse system (15-day-old B6C3F1 mice) by a single carcinogenic dose of diethylnitrosamine (2.5 or 5.0 micrograms/g body weight), were characterized histochemically using toluidine blue, periodic acid-Schiff, glycogen phosphorylase, glycogen synthetase, glucose-6-phosphatase, glucose-6-phosphate dehydrogenase, glyceraldehyde-3-phosphate dehydrogenase, ATPase, gamma-glutamyl transpeptidase, and acid phosphatase. Animals were killed 5, 12, 18, and 24 weeks following diethylnitrosamine treatment. The first focal lesions were observed in mice killed at 12 weeks. All foci showed patchy cytoplasmic basophilia and a slight decrease in the glycogen content. The early foci (12 weeks) showed no change in the levels of glycogen phosphorylase and glycogen synthetase, a strong reduction of glucose-6-phosphatase, and a high increase in glucose-6-phosphate dehydrogenase. In addition, 56% of foci in males and 86% of foci in females showed a slight rise in glyceraldehyde-3-phosphate dehydrogenase, and 12% of foci in males and 17% of foci in females had a lower acid phosphatase. The level of cytoplasmic ATPase was slightly decreased in 22% of foci. By 24 weeks, a decrease in the activity of cytoplasmic ATPase was observed in 84 and 100% of foci in males and females, respectively. The increase in the membrane ATPase was observed in 65% of foci in males and 7% of foci in females. By that time, the decrease in acid phosphatase was observed in 78% of foci in males and 37% of foci in females. The gamma-glutamyl transpeptidase failed to show any increase in its activity, indicating that this enzyme was not a "marker" of the hepatocellular lesions developing under the experimental conditions. Strong decrease in glucose-6-phosphatase in association with a manifest increase in glucose-6-phosphate dehydrogenase and glyceraldehyde-3-phosphate dehydrogenase activities indicated a shift from gluconeogenesis to glycolysis. Since this metabolic shift occurred concurrently with an increase in the labeling indices and focal size, it appears that these changes act in concert, representing expression of the acquired functional and replicating potential of the focal cell population.
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PMID:Histochemical characterization of focal hepatic lesions induced by single diethylnitrosamine treatment in infant mice. 285 11

In rats treated orally with a single dose of aflatoxin B1 (5 mg/kg body weight) characteristic focal and nodular liver lesions developed which differed in their fine structure, enzyme histochemical pattern and growth behaviour from other types of carcinogen-induced hepatic foci and nodules described earlier. The foci were composed of a distinct cell population which showed specific structural changes of the cytoplasm. Typically, unusually large and abundant basophilic bodies consisting of highly ordered stacks of cisternae of the rough endoplasmic reticulum (ER) were arranged in long, striped bands and stood out against an acidophilic background which was due to hypertrophy of the smooth ER. We propose the descriptive terms 'tigroid cells', and 'tigroid cell foci' for this population of altered hepatocytes. Correlative cytochemical investigations on the tigroid cell foci revealed characteristic changes in carbohydrate metabolism, such as a decrease in the activity of glycogen synthetase and glycogen phosphorylase and an increase in the activity of glucose-6-phosphate dehydrogenase and glyceraldehyde-3-phosphate dehydrogenase. The activity of glucose-6-phosphatase and ATPase was normal (or partially reduced) and that of the gamma-glutamyl-transpeptidase was always lacking. A progressive increase in the number and size of the tigroid cell foci and transitions from tigroid cell foci to neoplastic nodules with similar morphological and cytochemical features were observed during the time period of 104 weeks. The mitotic index within tigroid cell foci and nodules was approximately 100 times higher than that of the surrounding hepatic tissue or the liver parenchyma of untreated control animals. The important question whether the tigroid cell foci represent a specific pre-neoplastic or early neoplastic cell population requires further investigations.
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PMID:Tigroid cell foci and neoplastic nodules in the liver of rats treated with a single dose of aflatoxin B1. 286 15

Renal tubular lesions induced in male rats by two different carcinogens, N-nitrosomorpholine (NNM) and N-ethyl-N-hydroxyethylnitrosamine (EHEN), using a limited exposure "stop" protocol were investigated histochemically to demonstrate phenotypic cellular changes. The parameters measured included basophilia, glycogen content and the activity of the enzymes glucose-6-phosphatase (G6PASE), glycogen synthetase (SYN), glycogen phosphorylase (PHO), glucose-6-phosphate dehydrogenase (G6PDH), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), succinate dehydrogenase (SDH), alkaline phosphatase (ALP), acid phosphatase (ACP) and gamma-glutamyl transpeptidase (gamma-GT). The lesions observed were predominantly of either basophilic or oncocytic types. In each case, tubular lesions (altered tubules) appeared to give rise to epithelial tumors (epitheliomas) with the same cellular phenotype. Basophilic tubules and epitheliomas proved to be strongly positive for GAPDH and G6PDH while demonstrating a reduction or loss of G6PASE, ALP, ACP, gamma-GT, and SDH compared with controls and the surrounding proximal or distal tubules. In addition, large basophilic epitheliomas demonstrated an increase in both SYN and PHO activities. In contrast, most oncocytic tubules and oncocytomas characterized by abundant densely granular cytoplasm showed a reduction in the activity of G6PDH, but were intensely positive for SDH. However, a few oncocytic lesions demonstrated a decrease in both SDH and G6PDH activity. Rarely, decreased SDH and elevated G6PDH activities were observed in altered tubules resembling oncocytic tubules. It remains to be clarified whether these tubules represent a variation of the oncocytic lesions or, perhaps, another type of tubular lesion. The results indicate that basophilic and oncocytic epithelial tumors differ in their cytochemical pattern and histogenesis. In line with earlier suggestions, the basophilic tumors apparently originate from the proximal renal tubules, while the oncocytomas develop from the distal parts of the nephron. The basophilic tumors are characterized by an increased pentose phosphate pathway and glycolysis, with a corresponding reduction in mitochondrial respiration. However, the majority of the oncocytomas show an increased activity of the mitochondrial enzyme SDH, and a marked decrease in the activity of the key enzyme of the pentose phosphate pathway.
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PMID:Correlative histochemical studies on preneoplastic and neoplastic lesions in the kidney of rats treated with nitrosamines. 287 45


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