Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P17174 (aspartate aminotransferase)
 14,872 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Piscicidal activities of aqueous extracts of Euphorbia tirucalli were very well established, but their ultimate mode of action on fish metabolism was not yet known. Exposure of fishes over 24h or 96h to sub-lethal doses (40% and 80% of LC(50)) of aqueous extract of E. tirucalli stem-bark and latex, significantly (P<0.05) altered the level of total protein, total free amino acids, nucleic acids, glycogen, pyruvate, lactate and activity of protease, alanine aminotransferase, aspartate aminotransferase, acetylcholinesterase and cytochrome oxidase enzyme in liver and muscle tissues of freshwater fish Channa punctatus. The alterations in all these biochemical parameters were significantly (P<0.05) time- and dose-dependent. After 7d of withdrawal of treatment of 80% of LC(50) of E. tirucalli extracts shows that there was a partial recovery in the levels of glycogen but nearly complete recovery in total protein, total free amino acids, pyruvate, lactate, nucleic acids level and activity of protease, aspartate aminotransferase, alanine aminotransferase, acetylcholinesterase and cytochrome oxidase enzyme in both the tissues of fish. Thus aqueous extracts of E. tirucalli adversely affect respiratory pathway of fish and cause energy crisis during stress by suppressing ATP production. The reversibility of the action of the aqueous extracts would be an additional advantage in their use.
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PMID:Biochemical stress response in freshwater fish Channa punctatus induced by aqueous extracts of Euphorbia tirucalli plant. 1642 80

Reamberin in a dose of 25 mg/kg (succinate concentration) was injected intravenously for 3 days starting from the 1st hour after skin ischemia modeling. This treatment decreased activities of lactate dehydrogenase, aspartate transaminase, and creatine phosphokinase in skin homogenates by 1.6 times, 19%, and 51.3%, respectively. The index of cytolysis decreased by 18%. Reamberin had an energotropic effect, which manifested in an increase in the total ATP content and concentration of creatine phosphate (by 16 and 10%, respectively). After administration of Reamberin, activity of the succinate-ubiquinone reductase system increased by 17%. Under these conditions succinate dehydrogenase activity exceeded the normal by 21%. Reamberin had no effect on the mitochondrial NADH-ubiquinone reductase system in dermal cells during skin ischemia. Superoxide dismutase activity in the area of necrosis increased to the control level on day 3 of treatment with Reamberin. Activities of catalase and glutathione peroxidase increased by 13 and 19%, respectively. Our results indicate that the course of intravenous treatment with Reamberin for 3 days contributes to an increase in reserve capacities of the antioxidant protection system and produces a protective effect during skin ischemia.
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PMID:Protective effect of reamberin on functional activity of mitochondria during skin ischemia. 1667 75

Increasing evidence suggests an association between elevated serum aminotransferase level and the metabolic syndrome. However, the significance of relatively low levels of aminotransferase in relation to the metabolic syndrome has not been fully investigated in the general population. We investigated the association between serum amiontransferase level and the metabolic syndrome using data from a nationwide survey in Korea. We measured serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels and metabolic conditions among 9771 participants aged 20 or more in the 1998 and 2001 Korean National Health and Nutrition Examination Surveys. Metabolic syndrome was defined according to NCEP-ATP III criteria with a modified waist circumference cutoff (men > 90 cm; women > 80 cm). Serum aminotransferase level, even within normal range, was associated with the metabolic syndrome independent of age, body mass index, waist circumference, smoking, and alcohol intake. Compared with the lowest level (< 20 IU/L), the adjusted odds ratios (95% CI) for an AST level of 20-29, 30-39, 40-49 and > or = 50 IU/L were 1.10 (0.85-1.42), 1.37 (1.02-1.83), 1.62 (1.08-2.43), and 2.25 (1.47-3.44) in men, and 1.18 (0.99-1.41), 1.43 (1.29-1.83), 1.71 (1.09-2.68), and 2.14 (1.20-3.80) in women, respectively. Corresponding odds ratios for ALT levels were 1.27 (0.99-1.63), 1.69 (1.28-2.23), 2.17 (1.58-2.99), and 2.65 (1.96-3.58) in men, and 1.44 (1.22-1.70), 1.65 (1.26-2.15), 2.94 (1.93-4.47), and 2.25 (1.54-3.30) in women, respectively. In conclusion, elevated serum aminotransferase levels, even in the normal to near normal range, are associated with features of the metabolic syndrome.
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PMID:Normal serum aminotransferase levels and the metabolic syndrome: Korean National Health and Nutrition Examination Surveys. 1694 45

Since the 1980's nitric oxide (NO), carbon monoxide (CO) and hydrogen sulfide (H(2)S), the endogenous gas molecules produced from metabolic pathway, have been realized as signal molecules to be involved in the regulation of body homeostasis and to play important roles under physiological and pathophysiological conditions. The researches on these endogenous gas signal molecules opened a new avenue in life science. To explore the new member of gasotransmitter family, other endogenous gas molecules which have been regarded as metabolic waste up to date, and their biological regulatory effects have been paid close attention to in the current fields of life science and medicine. Sulfur dioxide (SO(2)) can be produced endogenously from normal metabolism of sulfur-containing amino acids. L-cysteine is oxidized via cysteine dioxygenase to L-cysteinesulfinate, and the latter can proceed through transamination by glutamate oxaloacetate transaminase (GOT) to beta-sulfinyl pyruvate which decomposes spontaneously to pyruvate and SO(2). In mammals, activated neutrophils by oxidative stress can convert H(2)S to sulfite through a reduced form of nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase-dependent process. The authors detected endogenous production of SO(2) in all cardiovascular tissues, including in heart, aorta, pulmonary artery, mesenteric artery, renal artery, tail artery and the plasma SO(2) content. As the key enzyme producing SO(2), GOT mRNA in cardiovascular system was detected and found to be located enriched in endothelial cells and vascular smooth muscle cells near the endothelial layer. When the normal rats were treated with hydroxamate(HDX), a GOT inhibitor, at a dose of 3.7 mg/kg body weight, the blood pressure (BP) went high markedly, the ratio of wall thickness to lumen radius was increased by 18.34%, and smooth muscle cell proliferation was enhanced. The plasma SO(2) level in the rats injected with 125 micromol/kg body weight SO(2) donor was increased to 721.98+/-30.11 micromol/L at the end of 30 seconds, while the blood pressure was decreased to the lowest point 65.0+/- 4.9 mm Hg at the end of 1 minute. The above results showed that endogenous SO(2) might be involved in the maintenance of blood pressure and normal vascular structure. In spontaneous hypertensive rat (SHR) animal model, exogenous supplement of SO(2) donor decreased the BP, the media cross-sectional area, and pressure of the media and the ratio of wall thickness to lumen radius in the SHR. Moreover, the proliferative index of aortic smooth muscle cells was decreased in the SHR treated with SO(2) donor compared with that in SHR. The above data showed that SO(2) could prevent the aortic structural remodeling by inhibiting the proliferation of aortic smooth muscle cells. The authors observed the direct vasorelaxant effects of SO(2) on the aortic ring pre-treated with norepinephrine (NE). SO(2) donor at a concentration of 25-100 micromol/L relaxed the aortic ring temporarily and slightly, but SO(2) donor at a concentration of 1-12 mmol/L induced relaxation of the ring in a concentration-dependent manner. Administration with nicardipine, an L-type calcium channel blocker other than glibenclamide, an ATP sensitive potassium channel (K(ATP) channel) blocker or removal of vascular endothelium could decrease the SO(2)-induced vasorelaxation. In hypoxic pulmonary hypertension animal model, SO(2) donor decreased the mean pulmonary artery pressure and the systolic pulmonary artery pressure (P<0.01), respectively as compared with hypoxic group, and alleviated obviously the hypoxic pulmonary vascular structural remodeling. The percentage of muscularized arteries of small pulmonary vessels was significantly decreased in hypoxia+SO(2) donor-treated rats compared with that of hypoxic rats (P<0.01), while the percentage of non-muscularized vessels was obviously higher in hypoxia with SO(2) donor-treated rats than that of hypoxic rats (P<0.01). Similarly, SO(2) obviously decreased relative media area and relative media thickness of small muscularized pulmonary arteries in hypoxic rats (P<0.01). The above data showed that SO(2) might play an important role in development of hypoxic pulmonary hypertension. Perfusion with SO(2) donor (10(-6)-10(-3) mol/L) to the isolated rat heart obviously inhibited the left ventricular peak rate of contraction ( + LV dp/ dtmax) , peak rate of relaxation (-LV dp/ dtmax) and difference of left ventricular pressure ( DeltaLVP) in a concentration dependent manner. Nicardipine, an L-type calcium channel blocker, could partly antagonize the inhibitory effect of SO(2) on the heart function. In a word, SO(2) could be endogenously generated in cardiovascular tissues and exert important cardiovascular effects such as vasorelaxant effect and negative inotropic effects. Moreover, SO(2) might play considerable roles in the regulation of systemic circulatory pressure, pulmonary circulatory pressure and vascular structural remodeling in the pathogenesis of hypertension and hypoxic pulmonary hypertension. On the basis of the above findings, we presumed that endogenous SO(2) might be a novel cardiovascular functional regulatory gasotransmitter. More studies on the significance of endogenous SO(2) in cardiovascular system under physiological and pathophysiological conditions need to be investigated.
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PMID:[Significance of endogenous sulfur dioxide in the regulation of cardiovascular system]. 1765 74

The final step of protein translocation across the mitochondrial inner membrane is mediated by a translocation motor composed of 1) the matrix-localized, ATP-hydrolyzing, 70-kDa heat shock protein mHsp70; 2) its anchor to the import channel, Tim44; 3) the nucleotide exchange factor Mge1; and 4) a J-domain-containing complex of co-chaperones, Tim14/Pam18-Tim16/Pam16. Despite its essential role in the biogenesis of mitochondria, the mechanism by which the translocation motor functions is still largely unknown. The goal of this work was to carry out a structure-function analysis of the mitochondrial translocation motor utilizing purified components, with an emphasis on the formation of the Tim44-mHsp70 complex. To this end, we purified Tim44 and monitored its interaction with other components of the motor using cross-linking with bifunctional reagents. The effects of nucleotides, the J-domain-containing components, and the P5 peptide (CALLSAPRR, representing part of the mitochondrial targeting signal of aspartate aminotransferase) on the formation of the translocation motor were examined. Our results show that only the peptide and nucleotides, but not J-domain-containing proteins, affect the Tim44-mHsp70 interaction. Additionally, binding of Tim44 to mHsp70 prevents the formation of a complex between the latter and Tim14/Pam18-Tim16/Pam16. Thus, mutually exclusive interactions between various components of the motor with mHsp70 regulate its functional cycle. The results are discussed in light of known models for the function of the mitochondrial translocation motor.
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PMID:The interplay between components of the mitochondrial protein translocation motor studied using purified components. 1788 57

We investigated the antiischemic properties of a new compound N-benzyl-N'-(2-hydroxy-3,4-dimethoxybenzyl)-piperazine (BHDP), having high affinity and selectivity for the sigma(1) receptor, in two different models of ischemia. The first was an experimental model of rat liver normothermic ischemia-reperfusion. Rats were pretreated with different doses of BHDP (0.5, 2.5 or 10 mg/kg/day, or solvent alone) and subjected to 90 min normothermic ischemia followed by either 30 or 120 min reperfusion. The second model was a hypothermic model of ischemia in which livers were incubated for 24 h at 4 degrees C in a preservation solution in the absence or presence of increasing BHDP concentrations (0.5, 2.5 or 10 microg/ml). These different ischemic conditions induced huge alterations in hepatocyte functions (membrane leakage of alanine aminotransferase and aspartate aminotransferase, decreased metabolic capacities evaluated by the ability of the liver to transform lidocaine, alterations of mitochondrial functions characterized by a decrease in ATP synthesis and the appearance of histological damages). Pretreatment of rats with BHDP alleviated these deleterious ischemia-reperfusion effects in a dose-dependent manner at both the cellular and mitochondrial levels. The protection of mitochondrial functions was almost complete at a dosage of 10 mg/kg/day during normothermic ischemia and 10 microg/ml in the preservation liquid during hypothermic ischemia. In addition, BHDP significantly reduced the histological damage. These data demonstrate that BHDP protects liver against the deleterious effects of ischemia-reperfusion and suggest that sigma(1) receptors play an important role in the protective effect.
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PMID:Protection of cellular and mitochondrial functions against liver ischemia by N-benzyl-N'-(2-hydroxy-3,4-dimethoxybenzyl)-piperazine (BHDP), a sigma1 ligand. 1796 67

Mitochondria are involved in the development of organ failure in critical care diseases. However, the mechanisms underlying mitochondrial dysfunction are not clear yet. Inducible hemoxygenase (HO-1), a member of the heat shock protein family, is upregulated in critical care diseases and considered to confer cytoprotection against oxidative stress. However, one of the products of HO-1 is Fe2+ which multiplies the damaging potential of reactive oxygen species catalyzing Fenton reaction. The aim of this study was to clarify the relevance of free iron metabolism to the oxidative damage of the liver in endotoxic shock and its impact on mitochondrial function. Endotoxic shock in rats was induced by injection of lipopolysaccharide (LPS) at a dose of 8 mg/kg (i.v.). We observed that the pro-inflammatory cytokine TNF-alpha and the liver necrosis marker aspartate aminotransferase were increased in blood, confirming inflammatory response to LPS and damage to liver tissue, respectively. The levels of free iron in the liver were significantly increased at 4 and 8 h after onset of endotoxic shock, which did not coincide with the decrease of transferrin iron levels in the blood, but rather with expression of the inducible form of heme oxygenase (HO-1). The proteins important for sequestering free iron (ferritin) and the export of iron out of the cells (ferroportin) were downregulated facilitating the accumulation of free iron in cells. The temporarily increased concentration of free iron in the liver correlated with the temporary impairment of both mitochondrial function and tissue ATP levels. Addition of exogenous iron ions to mitochondria isolated from control animals resulted in an impairment of mitochondrial respiration similar to that observed in endotoxic shock in vivo. Our data suggest that free iron released by HO-1 causes mitochondrial dysfunction in pathological situations accompanied by endotoxic shock.
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PMID:A novel endotoxin-induced pathway: upregulation of heme oxygenase 1, accumulation of free iron, and free iron-mediated mitochondrial dysfunction. 1798 71

Peripheral blood CD4+ adenosine triphosphate [ATP (ng/mL)] release [ImmuKnow Immune Cell Function Assay (ATP)] correlates to immunoreactivity. We hypothesized that ATP levels could provide insight into hepatitis C virus (HCV) infection and recurrent liver disease in liver transplantation (LT). We studied our center's LT cohort, in which ATP levels had been measured off protocol from February 2005 through July 2006. Of the 280 LTs performed since 1993, 114 (58.2%) fit the selection criteria, with a mean age of 49 +/- 10 years. LT (alone/combination) indications included HCV (58%), alcoholic liver disease (41%), hepatocellular carcinoma (16%), and other (33%). Four hundred seventy-seven ATP levels were obtained: 3 (1-17) per patient 25 months (4 days to 19 years) from the time from transplantation. Final diagnoses were normal allograft function (n = 166, 35%), recurrent disease (n = 199, 42%), septic event (n = 34, 7%), other (n = 51, 11%), and undetermined (n = 27, 6%). Two hundred eighty-one ATP levels were obtained [3 (1-18) per patient] in 66 HCV(+) patients. Forty-five (68%) developed biopsy-proven recurrent liver disease [188/281 (67%) ATP levels]. The median ATP level (ng/mL) was 162 (1-761); it was lower in HCV(+) patients (151 +/- 109) versus HCV(-) patients (211 +/- 139; P < 0.0001). ATP ranges in HCV(+) patients were stable from the time from transplantation. In HCV(-) patients, ATP ranges were initially high and eventually decreased to HCV(+) levels (P = 0.01). Immunosuppressant levels were low in 62% of HCV(-) patients versus 38% of HCV(+) patients (P = 0.04). In HCV(+) patients, ATP was lower in disease recurrence (139 +/- 97) versus none (181 +/- 141; P = 0.01) with similar immunosuppression, and ATP decreased with grade (P = 0.05) but not stage. Time from transplantation, aspartate aminotransferase/alanine aminotransferase >1, and low ATP were independently associated with recurrent HCV. In conclusion, after LT, global cellular immune function appears depressed at baseline in HCV(+) patients versus HCV(-) patients and more so in HCV(+) recurrent disease.
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PMID:Monitoring peripheral blood CD4+ adenosine triphosphate activity in a liver transplant cohort: insight into the interplay between hepatitis C virus infection and cellular immunity. 1875 85

Derivatives of Escherichia coli C were previously described for succinate production by combining the deletion of genes that disrupt fermentation pathways for alternative products (ldhA::FRT, adhE::FRT, ackA::FRT, focA-pflB::FRT, mgsA, poxB) with growth-based selection for increased ATP production. The resulting strain, KJ073, produced 1.2 mol of succinate per mol glucose in mineral salts medium with acetate, malate, and pyruvate as significant co-products. KJ073 has been further improved by removing residual recombinase sites (FRT sites) from the chromosomal regions of gene deletion to create a strain devoid of foreign DNA, strain KJ091(DeltaldhA DeltaadhE DeltaackA DeltafocA-pflB DeltamgsA DeltapoxB). KJ091 was further engineered for improvements in succinate production. Deletion of the threonine decarboxylase (tdcD; acetate kinase homologue) and 2-ketobutyrate formate-lyase (tdcE; pyruvate formate-lyase homologue) reduced the acetate level by 50% and increased succinate yield (1.3 mol mol(-1) glucose) by almost 10% as compared to KJ091 and KJ073. Deletion of two genes involved in oxaloacetate metabolism, aspartate aminotransferase (aspC) and the NAD(+)-linked malic enzyme (sfcA) (KJ122) significantly increased succinate yield (1.5 mol mol(-1) glucose), succinate titer (700 mM), and average volumetric productivity (0.9 g L(-1) h(-1)). Residual pyruvate and acetate were substantially reduced by further deletion of pta encoding phosphotransacetylase to produce KJ134 (DeltaldhA DeltaadhE DeltafocA-pflB DeltamgsA DeltapoxB DeltatdcDE DeltacitF DeltaaspC DeltasfcA Deltapta-ackA). Strains KJ122 and KJ134 produced near theoretical yields of succinate during simple, anaerobic, batch fermentations using mineral salts medium. Both may be useful as biocatalysts for the commercial production of succinate.
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PMID:Eliminating side products and increasing succinate yields in engineered strains of Escherichia coli C. 1878 96

Period 2 (Per2) is a key component of the core clock oscillator and is involved in regulating a number of different biological processes and pathways. Here we report that Per2 plays a protective role in carbon tetrachloride (CCl(4))-induced hepatotoxicity via the modulation of uncoupling protein-2 (Ucp2) gene expression in mice. Hepatic injury after acute CCl(4) injection was monitored in both wild-type and Per2-null mice. At the 12-hour time point after CCl(4) treatment, many more vacuolations were observed in the liver tissues of Per2-null mice whereas fatty tissue degeneration primarily occurred in the liver tissues of wide-type mice. Serum alanine and aspartate aminotransferase activities were elevated in Per2-null mice compared with wide-type mice at 24 hours after CCl(4) treatment, which was in agreement with the observation of significantly larger areas of centrilobular necrosis in the livers of Per2-null mice. A deficit of the Per2 gene enhanced Ucp2 gene expression levels in the liver. As a consequence, intracellular levels of ATP markedly decreased in the liver, allowing increased production of toxic CCl(4) derivatives. The absence of Per2 expression caused a dramatic elevation of Clock expression and influenced Ucp2 through a mechanism that involved a Clock-controlled PPAR-alpha signal transduction pathway. Our studies suggest that the Per2 gene functions in hepatocyte protection from chemical toxicants via the regulation of hepatic Ucp2 gene expression levels.
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PMID:The protective role of Per2 against carbon tetrachloride-induced hepatotoxicity. 1905 52


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