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:2.6.1.1 (aspartate aminotransferase)
21,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Abdominal neutrophils effect on rat skeletal muscle m. soleus was investigated in vitro. The incubation was carried out in Hanks balanced solution within 24 hrs. It was a release of proteins from m. soleus 1 hr later. Creatine kinase (CK) and aspartate aminotransferase (AAT) activities increase was detected in incubation medium. The neutrophils released their proteins quicker than muscles. A dramatic inhibition of CK and AAT activities took place during coincubation of m. soleus and neutrophils. Zymosan-activated cells had a higher inhibition potency in comparison to nonactivated neutrophils. Analysis of proteinase and myeloperoxidase activities in incubation medium has given evidence that CK and AAT inhibition by non-activated neutrophils mainly depends on cell-secreted proteinases. Zymosan-activated neutrophil inhibition of CK and AAT consists of proteinases and myeloperoxidase effects. AAT appeared to be more resistant than CK to the damage by neutrophils. The used approach failed to demonstrate the direct damage effect of neutrophils on m. soleus, but the described enzyme inhibition mechanism can take place in vivo during leukocyte infiltration of skeletal muscles after intensive muscular activity.
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PMID:[The mechanisms of the neutrophil suppression of creatine kinase and aspartate aminotransferase activities in rat skeletal muscles]. 129 86

This study was designed to examine the role of Kupffer cells in polymorphonuclear neutrophils (PMN) activation and infiltration after severe total hepatic ischemia. Male rats pretreated with either normal saline (NS group; n = 58) or gadolinium chloride (7 mg/kg; GC group, n = 57) for 2 days were subjected to 90 min total hepatic ischemia. In addition to 7-day survival rate, aspartate aminotransferase (AST), PMN liver infiltration, plasma myeloperoxidase (MPO), and interleukin-1 (IL-1) levels were serially measured from the end of ischemia to 360 min after reperfusion. Survival rate of the GC group significantly improved to 67% (P < 0.01), whereas that of the NS group remained at 20%. Extremely high AST levels (5,372 +/- 231 IU/liter) were obtained in the NS group, which correlated with the degree of hepatic necrosis. Very high IL-1 (270.3 +/- 91.2 pg/ml) and MPO (1.7 +/- 0.4 U/ml) levels were also seen in the NS group. The GC group significantly inhibited increases in AST, IL-1, and MPO levels as well as PMN infiltration in the liver compared to the NS group (P < 0.05). Our study demonstrated that Kupffer cell activation has an important role in the development of reperfusion injury after total hepatic ischemia through IL-1 release, and PMN activation and infiltration.
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PMID:Role of Kupffer cells in neutrophil activation and infiltration following total hepatic ischemia and reperfusion. 805 66

The purposes of this study were to clarify the role of neutrophilic proteases in the pathogenesis of hepatic ischemia/reperfusion injury and to determine whether urinary trypsin inhibitor (UTI) pretreatment attenuated liver ischemia/reperfusion injury in rats. Livers from male Sprague-Dawley rats were subjected to 90 min of no-flow warm ischemia followed by 120 min of reperfusion. Rats were divided into a UTI group and a control group. In the control group, 120-min reperfusion of the liver produced a significant increase in myeloperoxidase activity, a significant decrease in ATP and energy charge, and a marked increase in the serum aspartate aminotransferase, alanine aminotransferase, and lactic dehydrogenase levels. In the UTI group, the myeloperoxidase activity was significantly attenuated (P < 0.01), ATP and energy charge were significantly improved (P < 0.01 and P < 0.05, respectively), and the elevation in serum aspartate aminotransferase, alanine aminotransferase, and lactic dehydrogenase was also markedly suppressed (P < 0.05, P < 0.01, and P < 0.05, respectively) compared with the control group. Sections through the livers of control rats showed severe hepatocyte necrosis with neutrophil infiltration. In the UTI group, there was slight congestion and hepatocyte necrosis. The survival rate after 90-min liver ischemia was significantly improved compared with that in the control group (P < 0.05). The results of this study suggest that pretreatment with UTI significantly attenuates liver reperfusion injury, perhaps by inhibiting neutrophil proteases.
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PMID:Effect of protease inhibitor on ischemia/reperfusion injury of the rat liver. 827 98

We investigated whether anticoagulation would diminish ischemia-reperfusion injury of the liver. Liver ischemia was induced in rats by occluding the portal vein for 30 min. Anticoagulant was injected intravenously 10 min before occlusion. Serum concentrations of cytokine-induced neutrophil chemoattractant (CINC) in untreated rats increased following reperfusion, reaching a peak at 6 hr, then decreasing gradually to control levels by 24 hr. CINC levels in rats pretreated with heparin (50 units/kg), AT-III (250 units/kg), or DEGR-Xa (10 mg/kg) peaked at 3 hr after reperfusion and declined to baseline within 12 hr; peak CINC values were significantly lower than in untreated control rats. Expression of CINC mRNA in liver tissue paralleled the CINC serum levels. Both myeloperoxidase activity and the number of neutrophils in the liver were decreased in the anticoagulant groups. In addition, significant correlations were observed between the maximum values of AST, ALT, and LDH versus the peak CINC levels following ischemia-reperfusion. These results indicate that the release of CINC after ischemia-reperfusion of the liver is mediated by activation of coagulation within the hepatic microcirculation.
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PMID:Anticoagulant pretreatment attenuates production of cytokine-induced neutrophil chemoattractant following ischemia-reperfusion of rat liver. 868 28

Tissue injury is a common occurrence in multiple organ failure, a possible clinical complication of Gram-negative bacterial sepsis. Gram-negative bacteria, in part through lipopolysaccharide (LPS), tumor necrosis factor, and other cytokines, activate neutrophils to increase oxygen consumption and produce reactive oxygen species (ROS). ROS have been suggested to play a critical role in the pathogenesis of multiple organ failure. Accordingly, we hypothesized that the susceptibility of tissues to ROS can be reduced by augmenting the antioxidant status of the affected tissues. Rats were challenged intravenously with LPS (Escherichia coli: 0111:B4) at a dose of 1 mg/kg body weight, and 0, 2, 4, or 6 h later were treated intravenously with plain liposomes or alpha-tocopherol liposomes (20 mg alpha-tocopherol/kg body weight); treated rats were then killed 24 h after LPS challenge. Animals challenged with LPS were extensively damaged in the liver, as evidenced by an increase in plasma alanine aminotransferase and aspartate aminotransferase activities, and also in the lung, as indicated by a decrease in pulmonary angiotensin-converting enzyme and alkaline phosphatase activities. The injection of LPS also resulted in increased myeloperoxidase activities in the two organs, suggestive of activation of the inflammatory response. Within the pulmonary and hepatic organs of LPS-challenged animals, the involvement of oxidative stress mechanisms was evident, because a significant decrease in reduced glutathione and an increase in lipid peroxidation were observed. In contrast, the administration of alpha-tocopherol liposomes in the post-LPS-challenge period resulted in a significant alleviation of both lung and liver injuries, evidenced by a general reversal of the altered biochemical indices toward normal among treated animals. The therapeutic effect was found to be greater when liposomal alpha-tocopherol treatment was given earlier during the development of injury. Plain liposomes administered immediately after LPS injection also protected hepatic and pulmonary tissues from injuries. However, unlike alpha-tocopherol liposomes, plain liposomes did not confer any beneficial effect when administered at later timepoints post-LPS injection. These data suggest that alpha-tocopherol, administered in a liposomal form, may serve as a potentially effective pharmacological agent in the treatment of LPS-induced tissue injuries.
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PMID:Treatment of LPS-induced tissue injury: role of liposomal antioxidants. 882 99

Up-regulation of the leukocyte beta 2 integrin, CD18, is a key event in neutrophil-endothelial adhesion and neutrophil-mediated organ injury. Inhibition of CD18 with monoclonal antibodies reduces lung and liver neutrophil sequestration in animal models of Gram-negative bacteremia or endotoxemia. However, with a persistent septic challenge, interference with host leukocyte phagocytic defense could adversely affect outcome. To assess the effects of inhibiting CD18 on organ neutrophil responses, bacteremia, and organ injury after fecal peritonitis, mice underwent cecal ligation and puncture (CLP). At the time of CLP and 12 h later, mice received intravenous anti-CD18 antibody or control IgG. At 3, 6, and 18 h after CLP, lung and liver tissue neutrophil content were measured by myeloperoxidase (MPO) assay, peritoneal cells and blood leukocytes were differentially counted, blood was cultured, and serum aspartate aminotransferase was measured. There was a significant reduction in peritoneal neutrophil migration and an increase in blood neutrophils after anti-CD18 treatment compared with results from treatment with the control antibody. In the anti-CD18-treated group, liver MPO was increased fivefold at 6 and 18 h, while lung MPO was increased two-fold at 18 h when compared with the control antibody-treated group. The anti-CD18-treated group also had an increase in bacteria cultured from the blood at 6 and 18 h and an increase in serum aminotransferase at 18 h. Our data demonstrate that peritoneal neutrophil migration in response to an endogenous fecal challenge is CD18-dependent, and that this mechanism forms a vital part of host defense. Inhibition of CD18 increased neutrophil sequestration in the liver and lung and increased liver injury. This study demonstrates a paradoxical increase in organ neutrophil sequestration using a leukocyte anti-adhesion therapy during sepsis and suggests that anti-adhesion therapies targeted towards neutrophil may worsen outcome if given during an ongoing, localized infection.
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PMID:Inhibition of neutrophil migration at the site of infection increases remote organ neutrophil sequestration and injury. 937 66

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.
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PMID:Influence of postischemic administration of oxyradical antagonists on ischemic injury to rabbit skeletal muscle. 939 70

We investigated the protective effect of urinary trypsin inhibitor (ulinastatin: UTI) in vitro, in relation to the neutrophil activity in hepatic ischemia/reperfusion (I/R) injury. The rat liver was removed and preserved in cold Ringer's lactate solution for 60 min, followed by 120 min of reperfusion with oxygenated perfusate. The rats were divided into four groups (n = 8 in each group). The livers were perfused with Krebs-Henseleit (K-H) solution containing no additives in group 1, 50,000 U/kg of UTI in group 2, 3.5 x 10(6) of neutrophils in group 3, and both neutrophils and UTI in group 4. In group 3, the AST and ALT levels were always higher than those in other three groups at any point evaluated (P < 0.01) and the LDH levels were observed to be significantly higher than those in other three groups at 0, 5, 10, 60, and 90 min after reperfusion (P < 0. 01). These increase were suppressed by additional pretreatment with UTI in group 4. The bile flow during reperfusion was significantly suppressed in group 3 compared to that of group 4, at both 30 (P < 0. 01) and 60 (P < 0.05) min after reperfusion. The MPO activity after reperfusion in group 3 also significantly increased compared to other three groups (P < 0.01). These data thus suggest that UTI ameliorated the ischemia/reperfusion injury in vitro by inhibiting of neutrophil accumulation in the postischemic liver.
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PMID:Protective effects of ulinastatin against ischemia-reperfusion injury. 1006 23

Patients with homozygous (PiZ) alpha(1)-antitrypsin (AAT) deficiency have not only low baseline serum AAT levels (approximately 10 to 15% normal) but also an attenuated acute phase response. They are susceptible to the development of premature emphysema but may also be particularly susceptible to lung damage during bacterial exacerbations when there will be a significant neutrophil influx. The purposes of the present study were to assess the inflammatory nature of acute bacterial exacerbations of chronic obstructive pulmonary disease (COPD) in subjects with AAT deficiency, to compare this with COPD patients without deficiency, and to monitor the inflammatory process and its resolution following appropriate antibacterial therapy. At the start of the exacerbation, patients with AAT deficiency had lower sputum AAT (p < 0.001) and secretory leukoprotease inhibitor (SLPI; p = 0.02) with higher elastase activity (p = 0.02) compared with COPD patients without deficiency. Both groups had a comparable acute phase response as assessed by C-reactive protein (CRP) but the AAT-deficient patients had a minimal rise in serum AAT (to < 6 microM). After treatment with antibiotics, in patients with AAT deficiency, there were significant changes in many sputum proteins including a rise in SLPI levels, and a reduction in myeloperoxidase (MPO) and elastase activity (p < 0. 005 for all measures); the sputum chemoattractants interleukin-8 (IL-8) and leukotriene B(4) (LTB(4)) fell (p < 0.01), and protein leak (sputum/serum albumin ratio) became lower (p < 0.01). The changes were rapid and within 3 d of the commencement of antibiotic therapy the biochemical markers had decreased significantly, but took a variable time thereafter to return to baseline values. In conclusion, patients with AAT deficiency had evidence of increased elastase activity at the start of the exacerbation when compared with nondeficient COPD patients which probably reflects a deficient antiproteinase screen (lower sputum AAT and SLPI). The increased bronchial inflammation at presentation resolved rapidly with 14 d of antibiotic therapy.
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PMID:Evidence for excessive bronchial inflammation during an acute exacerbation of chronic obstructive pulmonary disease in patients with alpha(1)-antitrypsin deficiency (PiZ). 1058 15

There has been a widespread impression that tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) mediate the toxicity of high doses of lipopolysaccharide (LPS, endotoxin) and are key factors in septic shock. However, the clinical efficacy of treatment with antagonists of TNF-alpha and IL-1beta is still controversial, suggesting that mediators other than TNF-alpha and IL-1beta might contribute causally to endotoxin-induced death. Recent studies implicated high mobility group-1 (HMG-1) protein as a late mediator of endotoxin lethality in mice. However, the role of HMG-1 in mediating multiple organ damage-associating trauma has not been studied. This study was designed to investigate changes in HMG-1 gene expression in vital organs, and its potential role in mediating multiple organ damage following major burns. Wistar rats were subjected to a 35 percent full-thickness thermal injury, and randomly divided into three groups as follows: normal controls (n = 7), thermal injury (n = 24), and recombinant bactericidal/permeability-increasing protein (rBPI21) treatment (n = 12). Tissue samples from liver and lungs were collected to measure tissue endotoxin levels and HMG-1 mRNA expression. In addition, blood samples were obtained for measurement of organ function parameters. Our data demonstrated a significant increase in HMG-1 gene expression in tissues at 24 h postburn, which remained markedly elevated up to 72 h after thermal injury (P< 0.05-0.01). Treatment with rBPI21 could significantly decrease tissue HMG-1 mRNA expression in the liver and lung (P < 0.01). In addition, there were high positive correlations between hepatic HMG-1 mRNA and serum aminoleucine transferase (ALT) and aspartate aminotransferase (AST) levels, and also between pulmonary HMG-1 mRNA and myeloperoxidase activities (P < 0.05-0.01). Taken together, these findings indicate that thermal injury per se can markedly enhance HMG-1 gene expression in various organs. Up-regulation of HMG-1 expression may be involved in the pathogenesis of endogenous endotoxin-mediated multiple organ damage secondary to major burns.
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PMID:The significance of changes in high mobility group-1 protein mRNA expression in rats after thermal injury. 1195 36


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