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:2.6.1.2 (alanine aminotransferase)
26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Treatment of male guinea-pigs daily with an oral dose of 2 mg dehydroepiandrosterone (DHA) sulphate/100 g body weight for 2 weeks significantly reduced the glucose-6-phosphate dehydrogenase (G-6-PDH) activity of erythrocytes, liver, kidney and testis. Lactate dehydrogenase activity in plasma also decreased, but L-aspartate: 2-oxoglutarate aminotransferase (GOT) and L-alanine:2-oxoglutarate aminotransferase (GPT) activity in plasma remained unaffected. In liver and kidney, however, a significant rise in GOT and GPT was observed. A 2- to 3-7-fold increase of C19-steroids was observed in plasma, liver and kidney. In extracts of liver and kidney more than 60% of steroids were isolated from the sulphatide fraction. Only minor changes were detected in the metabolic pattern of C19-steroids, 17-hydroxysteroids prevailing in the free and sulphatide fractions, while 17-oxosteroids predominated in the sulphate and glucuronide fractions. A slight rise of cyclic AMP concentrations in liver and kidney tissue was attributed to the inhibition of phosphodiesterase by the DHA/G-6-PDH system
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PMID:Effects of exogenous dehydroepiandrosterone sulphate on various enzymes and on steroid metabolism in the guinea-pig. 13 7

Using rat hepatocytes we confirmed our previous results that glucagon and beta-adrenergic agonists increased the enzyme activity of alanine aminotransferase (AAT) and propranolol abolished their effects. Only the enzyme activity was measured and other parameters like quantity of the enzyme or activation due to modification were not looked for. As in perfusion experiment phenylephrine and phenoxybenzamine (alpha-agonist and alpha-antagonist respectively) also alpha-antagonist respectively) also increased the AAT activity in isolated rat hepatocytes and propranolol reversed these effects. The additive effect of glucagon and phenoxybenzamine on AAT was also persistent in hepatocyte system. Fructose-1:6-bisphosphatase (Fru-P2-ase), another key enzyme in gluconeogenic pathway, was elevated by glucagon and other beta-adrenergic agonists both in liver perfusion and isolated hepatocyte experiments and was brought back to the normal level by propranolol. In this case also only the enzyme activity was measured and no other parameters were looked for. Unlike AAT this enzyme was not stimulated by phenylephrine or phenoxybenzamine. But AAT and Fru-P2-ase activities were increased significantly by adenylate cyclase activators like fluoride or forskolin. Thus, it appears that the regulation of fru-P2-ase by glucagon is purely a b-receptor mediated process whereas AAT activation shows a mixed type of regulation where some well known alpha-agonist and antagonists are behaving as beta-agonists. Results further indicate the presence of phosphodiesterase in hepatocyte membrane which was stimulated by glucagon and brought back to the normal level by propranolol. The different adrenergic compounds stated above, not only modified the activity of the above two enzymes but also stimulated glucose production by hepatocytes from alanine which was in turn abolished by propranolol as well as amino oxyacetate (AOA), a highly specified inhibitor of AAT. This confirm the participation of AAT in gluconeogenesis from alanine in liver. Forskolin and fluoride also increased the glucose production from alanine and showed additive effects with glucagon, phenylephrine and phenoxybenzamine.
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PMID:Effect of adrenergic agonists and antagonists on alanine amino transferase, fructose-1:6-bisphosphatase and glucose production in hepatocytes. 135 93

Bloodstream forms of Trypanosoma brucei have been screened for the presence of enzymes that could serve as markers for the plasma membrane, flagellar pocket, lysosomes, endoplasmic reticulum and Golgi apparatus in order to study the subcellular organization of the digestive system of the parasite. Acetylesterase, acid DNase, acid phosphatase, acid phosphodiesterase, acid proteinase, acid RNase, alanine aminotransferase, galactosyl transferase, alpha-glucosidase, inosine diphosphatase and alpha-mannosidase were partially characterized and their assays optimized for pH-dependent activity, linearity of reaction with respect to incubation time and enzyme concentration, and the effect of inhibitors and activators. The association of these enzymes with particulate material and the presence of structural latency were investigated. Acid proteinase and alpha-mannosidase are particle-bound and latent in cytoplasmic extracts; they can be activated and solubilized in part by Triton X-100. Similar results were obtained for acid phosphatase, acid phosphodiesterase and inosine diphosphatase. Neutral alpha-glucosidase, though partly sedimentable, does not show latency and is readily solubilized by the detergent. Galactosyl transferase is firmly membrane-bound even in the presence of 0.1% Triton X-100. Cell fractionation by differential centrifugation and density equilibration on sucrose gradients revealed that both alpha-mannosidase and acid proteinase are associated with organelles that band at a density of about 1.20 g/cm3. Inosine diphosphatase, galactosyl transferase, acid phosphatase and acid phosphodiesterase sediment predominantly as microsomal constituents equilibrating at densities between 1.13 and 1.15 g/cm3. In addition, inosine diphosphatase and galactosyl transferase exhibit considerable activity at higher densities (1.18-1.25 g/cm3). Neutral alpha-glucosidase is mainly recovered in the nuclear and microsomal fraction; its particulate part equilibrates as a single band at rho = 1.22 g/cm3. Acetylesterase and acid DNase are largely soluble, whereas acid RNase does not produce distinct sedimentation and banding profiles. In intact cells, neutral alpha-glucosidase and acid phosphatase appear to be highly accessible to their substrates. It is tentatively concluded that (a) acid proteinase and alpha-mannosidase are lysosomal enzymes, (b) acid phosphatase and acid phosphodiesterase are associated with the flagellar pocket and part of the former enzyme probably with the endoplasmic reticulum, (c) galactosyl transferase is a constituent of the Golgi apparatus, and (d) alpha-glucosidase may serve as a marker for the plasma membrane. Inosine diphosphatase may also be derived from the latter structure.
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PMID:Subcellular fractionation of Trypanosoma brucei bloodstream forms with special reference to hydrolases. 624 76

The following study was performed to determine the effects of phosphodiesterase IV (PDE-IV) inhibition and its attenuation of tumor necrosis factor (TNF alpha) production in a rat model of the Adult Respiratory Distress Syndrome (ARDS). Rats were either unexposed (n = 8), pretreated orally with vehicle prior to intratracheal saline exposure (n = 11), pretreated with vehicle prior to 7 mg/kg intratracheal endotoxin (LPS) administration (n = 22), or pretreated with 5 or 50 mg/kg rolipram prior to LPS exposure (n = 6 and 7, respectively). Blood was sampled 1 and 3 hr post LPS exposure and assayed for plasma TNF alpha concentrations. Twenty-four hours after LPS exposure, blood was sampled again for hematologic measurements. The rats were then anesthetized and exsanguinated. Bronchoalveolar lavage (BAL) was performed after the lung of each rat was removed and weighed. Rolipram pretreatment was protective against LPS-induced mortality and also resulted in reduced plasma TNF alpha concentrations. LPS induced pulmonary edema, as indicated by wet/dry lung weight ratio (W/D) and total BAL protein content (TP) was attenuated by rolipram pretreatment. LPS-induced alveolar hemorrhage was reduced by rolipram pretreatment, but LPS-induced pulmonary neutrophilia was not. The hemoconcentration induced by LPS was reduced by rolipram, as was the LPS-induced thrombocytopenia. However, LPS-induced changes in circulating leukocyte populations were actually exacerbated by rolipram. LPS-induced alterations in renal and hepatic function, indicated by increased blood urea nitrogen (BUN), alanine aminotransferase (ALT), and aspartate aminotransferase (AST), were inhibited by rolipram.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Therapeutic intervention in a rat model of ARDS: IV. Phosphodiesterase IV inhibition. 838 94

Although intraportal infusion of adenosine suppressed the oxidative stress caused by activated neutrophils and attenuated ischemia-reperfusion injury of canine liver, high doses of adenosine elicit systemic hypotension. The present work demonstrates that combined use of low doses of adenosine and amrinone, a phosphodiesterase inhibitor, strongly inhibited reperfusion injury of the liver without eliciting hypotension. After 45 min ischemia followed by 60 min reperfusion of rat liver, low doses of adenosine and amrinone were administrated intraportally, resulting in significantly increased hepatic levels of cGMP, cAMP, nitrite plus nitrate in plasma, and decreased alanine aminotransferase in plasma without changing hemodynamics. Thus, intraportal administration of low doses of adenosine and amrinone increased the cyclic nucleotides, thereby improved microcirculation and attenuated reperfusion injury of the liver.
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PMID:Combined use of adenosine and amrinone inhibits reperfusion injury of rat liver. 1147 70

The two major metabolic perturbations resulting in hyperglycaemia in type 2 diabetes are insulin resistance and insulin deficiency. Insulin resistance occurs in peripheral organs (muscle and fat), leading to decreased glucose uptake and utilisation, and in liver, leading to increased hepatic glucose production. Thiazolidinediones, pharmacological ligands for PPAR gamma, can modulate the expression of genes influencing carbohydrate and lipid metabolism. Pioglitazone, a recently introduced thiazolidinedione, improves glycaemic control and lipid profiles in people with type 2 diabetes. Some of the possible mechanisms of improving glycaemic control include (a) increase in GLUT-1 and GLUT-4, (b) enhancement of insulin signalling, (c) decrease in tumour necrosis factor-alpha action, (d) reduction in plasma free fatty acid and (e) decrease in PEPCK. Together these can increase glucose uptake and utilisation in the peripheral organs and decrease gluconeogenesis in the liver. Possible mechanisms resulting in more desirable lipid profiles include an increase in phosphodiesterase-3B resulting in reduced intra-cellular lipolysis in adipocytes and an increase in lipoprotein lipase resulting in enhanced clearance of triglyceride-rich lipoproteins(TRLs). Pioglitazone, used as monotherapy or in combination with sulphonylurea, biguanide or insulin, improves glycaemic control, lowers serum triglycerides and raises high density lipoprotein (HDL)-cholesterol. It enhances hepatic and peripheral insulin sensitivity. In clinical trials, there has been no evidence of hepatotoxicity or increased incidence of elevated serum ALT in subjects taking pioglitazone compared with placebo.
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PMID:Current treatment of insulin resistance in type 2 diabetes mellitus. 1196 33

Adenosine is an important regulator of neuronal excitability. Zaprinast is a cyclic nucleotide phosphodiesterase inhibitor, and has been shown in the hippocampal slice to suppress excitation. This action can be blocked by an adenosine receptor antagonist, and therefore is presumably due to adenosine release stimulated by exposure to zaprinast. To explore the mechanism of this phenomenon further, we examined the effect of zaprinast on adenosine release itself in cultured rat forebrain neurons. Zaprinast significantly stimulated extracellular adenosine accumulation. The effect of zaprinast on adenosine appeared to be mediated by increasing intracellular cyclic adenosine monophosphate (cAMP) and activation of protein kinase A (PKA): (i) zaprinast stimulated intracellular cAMP accumulation; (ii) a cAMP antagonist (Rp-8-Br-cAMP) significantly reduced the zaprinast effect on adenosine; (iii) an inhibitor of phosphodiesterase (PDE)1 (vinpocetine) and an activator of adenylate cyclase (forskolin) mimicked the effect of zaprinast on adenosine. We also found that zaprinast had no effect on adenosine in astrocyte cultures, and tetrodotoxin completely blocked zaprinast-evoked adenosine accumulation in neuronal cultures, suggesting that neuronal activity was likely to be involved. Consistent with a dependence on neuronal activity, NMDA receptor antagonists (MK-801 and D-APV) and removal of extracellular glutamate by glutamate-pyruvate transaminase blocked the effect of zaprinast. In addition, zaprinast was shown to stimulate glutamate release. Thus, our data suggest that zaprinast-evoked adenosine accumulation is likely to be mediated by stimulation of glutamate release by a cAMP- and PKA-dependent mechanism, most likely by inhibition of PDE1 in neurons. Furthermore, regulation of cAMP, either by inhibiting cAMP-PDE activity or by stimulating adenylate cyclase activity, may play an important role in modulating neuronal excitability. These data suggest the existence of a homeostatic negative feedback loop in which increases in neuronal activity are damped by release of adenosine following activation of glutamate receptors.
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PMID:Elevation of intracellular cAMP evokes activity-dependent release of adenosine in cultured rat forebrain neurons. 1514 1

The study of erectile function in diabetic animal models has revealed physiological alterations in neural, vascular, hormonal and endothelial function. The aims of this review are to further elucidate pathophysiological changes induced by diabetes mellitus and to introduce new concepts in the study of erectile dysfunction (ED) in animal models. The recognized pathophysiological mechanisms causing diabetic ED include oxidative stress and hormonal imbalance. The evolving treatments for ED include advanced glycosylated endproduct (AGE) inhibitors, phosphodiesterase type 5 inhibitors, protein kinase C (PKC) inhibitors, hormone replacement, and gene transfer techniques. Our current understanding of how these multiple pathophysiological mechanisms contribute to ED is discussed. In this review, diabetic animal model studies have documented that oxidative stress is a pre-eminent pathophysiological mechanism and several anti-oxidants, such as alpha-lipoic acid, vitamin E, sodium selenate, melatonin, and ascorbic acid, reverse both neurogenic and endothelial dysfunction in diabetic models. Further, the peroxynitrite decomposition catalyst - FeTMPyP, PKC beta selective inhibitor - LY333531, I kappaB kinase 2 inhibitor - AS602868, AGE inhibitors - aminoguanidine and ALT-711 show promise by exploring different cellular mechanisms in treating diabetic problems. A number of vectors have been used to insert genes to increase the expression of nitric oxide synthase, superoxide dismutase, maxi-K channel (hSlo), neurotrophin-3, and vasoactive intestinal polypeptide for the treatment of erectile function. Further investigation of the hormonal treatment of diabetes associated with hypogonadism may improve sildenafil responsiveness in diabetic patients. We are optimistic that novel prevention and treatment strategies for diabetic ED are on the horizon.
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PMID:A critical appraisal of erectile function in animal models of diabetes mellitus. 1907 58

Chronic cholestasis and cholangitis may lead to the last phase known as biliary cirrhosis, characterized by cellular necrosis, apoptosis, tissue damage, local regeneration, inflammation and fibrosis. Such events are mediated by cytokines. Thalidomide and its analogs have shown to be effective immunomodulatory and hepatoprotective agents. The aim of this work was to evaluate the hepatoprotective properties of a thalidomide analog, the 3-phthalimido-3-(3,4-dimethoxyphenyl)-propanoic acid (PDA), on bile duct obstruction-induced cirrhosis. Vehicle or PDA (67 mg/kg) was orally administered twice a day to sham (Sham) or bile duct-ligated (BDL) male Wistar rats. The animals were sacrificed 28 days after treatments. Alkaline phosphatase (AP), gamma-glutamyl transpeptidase (GGTP) and alanine aminotransferase (ALT) enzyme activities as well as direct and total bilirubins concentration were determined in plasma. Lipid peroxidation (LP), glycogen and collagen were quantified in liver; in addition, histopathology was performed. PDA improved cholestasis, necrosis and fibrosis by significantly diminishing most of liver injury markers (P<0.05). Histopathology also showed remarkable liver damage amelioration. PDA effectiveness may be due to its water-solubility, stability, phosphodiesterase-4 inhibitory and immunomodulatory actions. Thalidomide and its analogs seem to be promising drugs for further treatment of biliary cirrhosis.
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PMID:The thalidomide analog 3-phthalimido-3-(3,4-dimethoxyphenyl)-propanoic acid improves the biliary cirrhosis in the rat. 1909 29

Scatophagus argus of the family Scatophagidae inflicts painful wounds in fishermen while handling it. The venom induces prominent local tissue damage characterized by pain, edema and necrosis. The pathogenesis of acute muscle damage in gastrocnemius muscle induced by S. argus venom was studied in mice. The inflammatory response induced by S. argus venom in the mice hind paw was studied measuring paw edema. Intramuscular injection of S. argus venom induced motoxicity. The effect of S. argus venom on the cellular components of inflammatory response was investigated. Venom from S. argus were quantitatively analyzed for enzymic and biochemical activity. The biochemical changes induced by the sublethal concentration of S. argus venom and histopathological studies of effect of venom on mice were carried out. Venom induced a rapid increment in serum creatine kinase (CK) and lactate dehydrogenase (LDH) showing the myotoxicity of venom. Concomitant with this a reduction of muscle CK and LDH activity was observed, where as no increment in muscle lactate was detected. Our findings showed that the edematic activity was dose dependent and remained significantly elevated over 48 h after injection. Administration of S. argus venom caused a significant cell accumulation of neutrophils in to peritoneal cavity as well as foot pad up to 24h with maximal being at 4-6h. The venom components analyzed showed the presence of phosphodiesterase, acid phosphatases, alkaline phosphatases, proteinase, and caseinolytic activity. SDS PAGE revealed the presence of major and minor protein bands between 6.5 and 68 kDa. The biochemical changes induced by the sublethal concentration of S. argus venom showed reversible changes in the hematological (blood cell count, hematocrit, hemoglobin, mean corpuscular volume, mean corpuscular hemoglobin and platelet count) parameters which were significantly altered at 6 and 24h (GLM repeated measures p<0.05). Serum enzymes such as AST, ALT, ACP, ALP, LDH and urea were altered significantly which in turn confirmed the damage of vital organ tissue.
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PMID:Characterization of biological activity of Scatophagus argus venom. 2060 40


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