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

The aim of this study was to determine whether the administration of free radical antagonists, immediately before and during the early minutes of reperfusion, improves muscle survival 24 hr after a period of ischemia. Rabbit rectus femoris muscles were isolated, made ischemic for 3 1/2 hr and treated with either desferrioxamine (DFX), an Fe3+ chelator, superoxide dismutase and catalase (SOD & CAT), which quench superoxide and hydrogen peroxide, or allopurinol, an inhibitor of xanthine oxidase (XO). After 24 hr reperfusion, muscle viability (+/-s.e.m.), measured by the nitro blue tetrazolium (NBT) vital staining technique, was 41.6 +/- 11.3% for saline-treated ischemic controls, 30.6 +/- 7.6% for DFX-treated, 46.7 +/- 10.3% for SOD & CAT-treated, and 43.3 +/- 9.5% for allopurinol-treated muscles. None of the treated groups differed significantly from the ischemic control group. Tissue myeloperoxidase, ATP and reduced glutathione levels, and plasma lactate dehydrogenase (LDH) and aspartate transaminase (AST) levels were increased by ischemia and reperfusion in all groups, but the changes did not differ between the treatment groups. Levels of XO in the rabbit muscle were determined and found to be very low in both normal and postischemic muscle. As XO is the target enzyme of allopurinol, its absence provides a basis for the lack of effect of this agent. However, it is not clear why DFX and SOD & CAT had no protective effect.
 ...
PMID:Influence of postischemic administration of oxyradical antagonists on ischemic injury to rabbit skeletal muscle. 939 70

The hepatocellular necrogenic and regenerative responses of newly weaned rats (21 days old) to a sublethal dose of thioacetamide (6.6 mmol kg-1) were studied in comparison to adult (6-month old rats), in terms of liver injury, antioxidant defense systems and cell proliferation. Hepatocellular necrosis, detected by serum aspartate aminotransferase, was less severe in newly weaned rats than in adult animals and was parallel to previous changes in the activity of microsomal FAD monooxygenase system responsible for thioacetamide biotransformation. Liver damage in hepatocytes from newly weaned rats was also detected by the decreased levels of glutathione and protein thiol groups (47%, p < 0.001 and 52%, p < 0.001 vs. untreated, respectively) and by the enhanced malondialdehyde production (334%, p < 0.001) and glutathione S-transferase activity (384%, p < 0.001). No significant differences were detected in these values when compared to adults. Changes in cytosolic and mitochondrial superoxide dismutase and catalase activities in hepatocytes from newly weaned rats at 24 h, following thioacetamide (49%, p < 0.001; 50% and 53%, p < 0.001 vs. untreated, respectively), were less severe against those in adult hepatocytes at 48 h of intoxication, and the increases in glutathione peroxidase and glutathione reductase activities were significantly lowered: 25% (p < 0.001) and 41% (p < 0.001), respectively. Post-necrotic DNA synthesis in hepatocytes from newly weaned rats peaked at 48 h of intoxication, while in adults a more intense peak appeared at 72 h preceded by a sharp decrease in tetraploid population. These differences indicate that the lower necrogenic response against the same dose of thioacetamide in newly weaned rats may be due to the lower rate of thioacetamide biotransformation and to the earlier onset of cell division. Accordingly, the growing liver from newly weaned rats presents advantages against the necrogenic aggression of thioacetamide, first, because the diminished activity of its specific microsomal detoxification system, and second because the earlier increase in the proliferative response prevents the progression of injury permitting an earlier restoration of liver function.
 ...
PMID:Necrogenic and regenerative responses of liver of newly weaned rats against a sublethal dose of thioacetamide. 960 62

Prevention of cellular damage after warm ischemia is of major importance in liver transplantation. In this study, we determined the extent to which lipid peroxides contribute to the pathogenesis of hepatic cell damage induced by transient warm ischemia with subsequent reperfusion. In addition, the function and immunohistochemical features of glutathione peroxidase, a potent physiological lipid peroxide scavenger of the liver, was assessed. Reperfusion following 15 or 30 minutes of warm ischemia resulted in a significant elevation in serum and liver lipid peroxidase (LPO) levels. In addition, necrosis of the hepatic periportal area accompanied with remarkable rises in serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were observed. In contrast, 30 min of ischemia without reperfusion caused minimal hepatocellular damage. The adverse changes after ischemia/reperfusion were minimized by pretreatment with superoxide dismutase (SOD). These results indicate that increased lipid peroxidation by production of radicals after reperfusion caused the liver cell damage. After ischemia/reperfusion, liver glutathione peroxidase (GSH-PO) activity was significantly decreased and its location altered in the damaged liver. These findings suggest that GSH-PO contributes significantly to the protection against hepatic reperfusion injuries.
 ...
PMID:Alterations in glutathione peroxidase activity following reperfusion injury to rat liver. 960 29

The role of nitric oxide (NO) on liver oxidative stress and tissue injury in rats subjected to tourniquet shock was investigated. This shock model differs from others in that injury is a consequence of remote organ damage. Liver oxidative stress becomes evident after hind limb reperfusion, as evidenced by the loss of total tissue thiols; by increases in tissue oxidized glutathione (GSSG), lipid peroxidation (LPO), plasma aminotransferases (alanine aminotransferase (ALT) and (aspartate aminotransferase (AST)), and plasma nitrites; and by a 36% loss in total superoxide dismutase (SOD) activity. Portal blood flow is reduced by 54.1% after 2 h of hind limb reperfusion. Inhibition of NO synthesis with Nomega-nitro-L-arginine methyl ester or L-arginine methyl ester increased mean arterial blood pressure; further reduced portal blood flow; and aggravated liver injury as assessed by further loss in total thiols, increased LPO and GSSG content, and further increases in plasma ALT and AST. Total plasma nitrites were lower than in control animals, and total tissue SOD activity decreased by more than 80%. Treatment with the NO donor sodium nitroprusside reverted the decrease in portal blood flow and also reverted tissue thiol loss, LPO, and GSSG increases, as well as the loss of ALT and AST to plasma and of SOD activity to levels comparable to untreated control shock animals. As expected, plasma nitrites were greater than in tourniquet control animals. These data support the hypothesis that endogenous NO formation protects the rat liver from the consequences of oxidative stress elicited by hind limb reperfusion in rats subjected to tourniquet shock.
 ...
PMID:Inhibition of nitric oxide synthesis aggravates hepatic oxidative stress and enhances superoxide dismutase inactivation in rats subjected to tourniquet shock. 961 80

Phenotypic characterization of 511 strains of Leishmania, subgenus Viannia, isolated from Colombian patients was conducted based on electrophoretic polymorphisms of 13 isoenzymes. Ninety-one Colombian strains of L. braziliensis were the most heterogeneous, constituting seven zymodemes while 397 L. panamensis and 22 L. guyanensis strains yielded five and three zymodemes, respectively. Phosphogluconate dehydrogenase, nucleoside hydrolase, and superoxide dismutase were the most polymorphic enzymes in this collection of strains, and together with glucose-6-phosphate dehydrogenase, allowed the discrimination of the three aforementioned species. Hierarchical cluster analysis of the zymodemes using Jaccard's coefficient of similarities revealed two clusters, one constituted by L. braziliensis zymodemes, and another by three subgroups consisting of zymodemes of L. panamensis closely related to the species reference strain, another consisting of L. guyanensis zymodemes, and a third group distinguished by new electromorphs of proline iminopeptidase and aspartate aminotransferase that reacted with the L. panamensis-specific monoclonal antibody B-11. Multiple zymodemes of L. panamensis and L. guyanensis were found to be sympatrically transmitted in foci along the Pacific coast. Leishmania braziliensis variants were ubiquitous throughout the territory of Colombia; L. panamensis was prevalent in the western region and L. guyanensis was prevalent in the Orinoco and Amazon river basins in the eastern half of the country. Distinct zymodemes of L. panamensis predominated in the northern and southern regions of the Pacific coast. Nine zymodemes of all three species were isolated from mucosal lesions. Zymodeme 1.1 of L. braziliensis had the highest frequency of mucosal involvement (10% of the cases), and disease caused by this zymodeme had the longest mean time of evolution (31 months; P = 0.002). In addition to being useful in describing epidemiologic relationships, the intraspecific heterogeneity of strains of the Viannia subgenus within and among foci can be used to understand such fundamental questions as the pathogenicity of different populations of parasites, and the induction of cross-protection against related parasites.
 ...
PMID:Epidemiologic, genetic, and clinical associations among phenotypically distinct populations of Leishmania (Viannia) in Colombia. 968 34

Age-associated changes in liver injury and post-necrotic regeneration were studied in rats aged 6 and 30 months in a period of 96 h following a dose of thioacetamide (6.6 mmol/kg body weight). Hepatocellular necrosis was detected in both groups by serum aspartate aminotransferase, but the severity of injury was significantly lower (one fourth, p < 0.001) in the oldest. Differences were observed in hepatocyte FAD monooxygenase activity between 6 and 30 months old rats at 24 h (278 versus 170%, p < 0.001, respectively) and also in GSH/GSSG ratio, in protein thiol groups and in malondialdehyde. Glutathione peroxidase, glutathione reductase and glucose-6-phosphate dehydrogenase activities rose markedly in both groups, this increase being slightly lower in the oldest. Superoxide dismutase and catalase did not show significant changes between both groups. At the end of the 96 h experimental period the restoration towards normal of GSG/GSSG, protein thiols malondialdehyde and the activities of Cu-Zn superoxide dismutase and catalase were significantly lower in hepatocytes from 30 months old rats. We summarize that the main age-related changes in the sequenced process of liver injury and regeneration occurred to a lesser extent in severity of injury and delayed response in the post-necrotic restoration of liver function, probably due to a lower increase in antioxidant enzyme system.
 ...
PMID:Aging delays the post-necrotic restoration of liver function. 969 17

We showed previously that supplementation for 30 d with 800 IU (727 mg) vitamin E/d did not adversely affect healthy elderly persons. We have now assessed the effects of 4 mo of supplementation with 60, 200, or 800 IU (55, 182, or 727 mg) all-rac-alpha-tocopherol/d on general health, nutrient status, liver enzyme function, thyroid hormone concentrations, creatinine concentrations, serum autoantibodies, killing of Candida albicans by neutrophils, and bleeding time in 88 healthy subjects aged >65 y participating in a double-blind, placebo-controlled trial. No side effects were reported by the subjects. Vitamin E supplementation had no effect on body weight, plasma total proteins, albumin, glucose, plasma lipids or the lipoprotein profile, total bilirubin, alkaline phosphatase, serum aspartate aminotransferase, serum alanine aminotransferase, lactate dehydrogenase, serum urea nitrogen, total red blood cells, white blood cells or white blood cell differential counts, platelet number, bleeding time, hemoglobin, hematocrit, thyroid hormones, or urinary or serum creatinine concentrations. Values from all supplemented groups were within normal ranges for older adults and were not significantly different from values in the placebo group. Vitamin E supplementation had no significant effects on plasma concentrations of other antioxidant vitamins and minerals, glutathione peroxidase, superoxide dismutase, or total homocysteine. There was no significant effect of vitamin E on serum nonspecific immunoglobulin concentrations or anti-DNA and anti-thyroglobulin antibodies. The cytotoxic ability of neutrophils against Candida albicans was not compromised. Thus, 4 mo of supplementation with 60-800 IU vitamin E/d had no adverse effects. These results are relevant for determining risk-to-benefit ratios for vitamin E supplementation.
 ...
PMID:Assessment of the safety of supplementation with different amounts of vitamin E in healthy older adults. 970 Nov 88

The purpose of this paper was to assess the role of continuous warm blood cardioplegia in heart valve replacement in comparison with standard intermittent cold crystalloid cardioplegia. Twenty patients undergoing open heart valve replacement were divided arbitrarily into two groups in this study; Group I was given intermittent perfusion of cold crystalloid (St. Thomas Hospital solution) with hypothermic cardiopulmonary bypass (CPB) (10 patients) and Group II was given continuous administration of warm blood cardioplegia with normothermic CPB (10 patients). The groups were similar with respect to sex, age, body surface area and preoperative ventricular function. Bypass conditions as well as perioperative complications were evaluated in the respective groups. Peak values of the serum enzyme levels within 120 hours of postoperation including alanine transaminase, aspartate aminotransferase, lactate dehydrogenase (LDH) and its isoenzymes LDH1 + LDH2, phosphokinase (CK) and its isoenzyme CK-MB, superoxide dismutase, and malondialdehyde in the two groups were also assessed. Biopsies from the right atrium were obtained immediately before aortic cross clamp removal (ischemic period), and 30 minutes after cross clamp removal (reperfusion period). Myocardial structures were observed and scored. No significant intergroup differences were found in the bypass conditions except for the perfusion flow, systemic temperature and central venous pressure. There were no significant differences in the intergroup perioperative complications, either. Serum enzymes except CK which reached peak values in Group I appeared prior to or consistent with Group II. There were no significant intergroup differences in peak levels of the serum enzymes except CK (307.44 +/- 38.56 U/L vs. 466.29 +/- 52.03 U/L, p = 0.039 for CK). From the pathological assessment, the structural alterations were the most severe during the reperfusion period in group I. Myocardial damage showed more severely in reperfusion than in ischemia in both. Warm blood cardioplegic technique, raising potential hazards, is still a practical method for myocardial protection in open heart surgery, but might be less effective in protecting the tissues beyond myocardium.
 ...
PMID:Benefits and pitfalls of warm blood cardioplegia in heart valve replacement: systemic protective effects. 981 3

Both serine hydroxymethyltransferase and aspartate aminotransferase belong to the alpha-class of pyridoxal-5'-phosphate (pyridoxalP)-dependent enzymes but exhibit different reaction and substrate specificities. A comparison of the X-ray structure of these two enzymes reveals that their active sites are nearly superimposable. In an attempt to change the reaction specificity of serine hydroxymethyltransferase to a transaminase, His 230 was mutated to Tyr which is the equivalent residue in aspartate aminotransferase. Surprisingly, the H230Y mutant was found to catalyze oxidation of NADH in an enzyme concentration dependent manner instead of utilizing L-aspartate as a substrate. The NADH oxidation could be linked to oxygen consumption or reduction of nitrobluetetrazolium. The reaction was inhibited by radical scavengers like superoxide dismutase and D-mannitol. The Km and kcat values for the reaction of the enzyme with NADH were 74 microM and 5. 2 x 10-3 s-1, respectively. This oxidation was not observed with either the wild type serine hydroxymethyltransferase or H230A, H230F or H230N mutants. Thus, mutation of H230 of sheep liver serine hydroxymethyltransferase to Tyr leads to induction of an NADH oxidation activity implying that tyrosyl radicals may be mediating the reaction.
 ...
PMID:A change in reaction specificity of sheep liver serine hydroxymethyltransferase. Induction of NADH oxidation upon mutation of His230 to Tyr. 1067 98

We report on the prooxidant (lipid peroxides) and antioxidant levels (ascorbic acid, reduced glutathione, superoxide dismutate activity) in healthy individuals (30) and patients with cirrhosis (37; 22 alcoholic cirrhosis and 15 non alcoholic cirrhosis). A significant increase in plasma lipid peroxide (P < 0.05) and ascorbic acid (P < 0.01) and a significant decrease in reduced glutathione (P < 0.001) and superoxide dismutase activity (P < 0.05) in haemolysate was observed in cirrhosis patients compared to the control group. A significant decrease in reduced glutathione (P < 0.01) and superoxide dismutase (P < 0.05) activity was also observed when the alcoholic cirrhosis group was compared to non alcoholic group. A significant increase in aspartate transaminase (P < 0.05), gamma glutamyl transaminase (P < 0.01) and aspartate transaminase/alanine transaminase (P < 0.05) ratio was seen in alcoholic cirrhosis group. A significant positive correlation between gamma glutamyl transferase and lipid peroxides (r = 0.48, P < 0.05) was observed in alcoholic cirrhosis.
 ...
PMID:Oxidative stress in alcoholic liver disease. 1070


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