Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.6.1.2 (alanine aminotransferase)
 26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An amino acid-based solution has been recently developed and has demonstrated significant protective effects during cold storage of small bowel (SB). This study was designed to examine the role of this novel solution in ameliorating intestinal injury in an in vivo model of ischemia-reperfusion (IR). The impact of luminal treatment with an amino acid-based (AA) solution was assessed throughout reperfusion after 60-min warm ischemia (WI) in rodent SB. Energetics (ATP and total adenylates) remained significantly elevated throughout 60-min reperfusion in AA-treated tissue compared with untreated controls. Increases in end-products (ammonia and alanine) and increases in alanine aminotransferase and glutaminase activity implicated greater amino acid metabolism in AA-treated tissues. After reperfusion, malondialdehyde levels were similar between all groups. Glutathione levels were consistently elevated in AA-treated tissues and by 60 min reperfusion values were sixfold greater than control. AA-mediated protection during IR resulted in reduced neutrophil infiltration suggesting a weaker inflammatory response. Barrier function and electrophysiology parameters exhibited a clear pattern of mucosal preservation in AA-treated tissues; histology supported these findings. This study raises the possibility of a role for a luminal nutrient-rich solution during ischemic storage of small bowel in the clinic.
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PMID:Alleviating ischemia-reperfusion injury in small bowel. 1508 67

The plastidial phosphoenolpyruvate (PEP)/phosphate translocator (PPT) is expressed in the developing embryos of oilseed rape (Brassica napus L.). PEP can be imported by plastids isolated from embryos and used for fatty acid synthesis at rates that are sufficient to account for one-third of the rate of fatty acid synthesis in vivo. This provides the first experimental evidence for uptake of PEP and incorporation of carbon from it into fatty acids by plastids. PEP metabolism in isolated plastids is able to provide some of the ATP required for fatty acid synthesis. Expression of the PPT and related glucose 6-phosphate (Glc-6-P) translocator (GPT) is high in early embryo and leaf development and then declines. The marked decline in the abundance of PPT and GPT transcripts between the pre- and mid-oil accumulating stages of embryo development in B. napus does not correlate with the corresponding translocator activities, which both increase over the same period. This means that transcript abundance cannot be used to infer the activity of the translocators.
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PMID:The import of phosphoenolpyruvate by plastids from developing embryos of oilseed rape, Brassica napus (L.), and its potential as a substrate for fatty acid synthesis. 1520 49

Fructose-1,6-bisphosphate (FBP) has been reported to have a protective effect on liver injury following ischemic/reperfusion periods. FBP maintains ATP levels and thereby cellular energy metabolism, which is important to the liver during cold preservation. In the present study, we evaluated the effects of FBP on the composition of storage solutions for cold liver preservation. Adult male Wistar rats were randomly divided into three experimental groups. Hepatic perfusion and preservation were performed with UW, UW plus 10 mmol/L FBP (UWM), and FBP 10 mmol/L (FBPS) alone solutions. Biochemical measurements of AST, ALT, and TBARS were performed on samples of the cold storage solution at 0, 12, 18, and 24 hours preservation. FBPS and UW solutions showed similar preservation grades during 18 hours. Addition of 10 mmol/L of FBP to UW solution induced liver injury and a poor preservation grade. FBP appears to protect the liver from injury caused by free radicals when the preservation time is less than 18 hours. Therefore, FBP may exert a protective effect for the preservation of livers during cold storage, and could represent an important component of new cold storage solutions.
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PMID:Protective effect of fructose-1,6-bisphosphate in the cold storage solution for liver preservation in rat hepatic transplantation. 1525 7

To elucidate the pathophysiological significance of adenosine 3'-monophosphate (3'-AMP) forming enzyme in rats, the effect of iron lactate overloading on the enzyme activities and adenine nucleotide levels in the liver and spleen was examined. Sprague-Dawley rats were fed a diet supplemented with 0%, 0.625% or 5.0% of iron lactate for 4 weeks. Iron deposition was found in periportal hepatocytes, Kupffer cells and macrophages of red pulp of the spleen. No significant changes in hematological parameters were detected. Although serum alkaline phosphatase and inorganic phosphorus levels elevated slightly in the 5.0% group, activities of alanine aminotransferase and aspartate aminotransferase, and levels of serum urea nitrogen and creatinine were not changed significantly. The ATP levels in the liver and spleen of iron fed groups were significantly decreased, but adenosine 5'-diphosphate (ADP) and adenosine 5'-monophosphate (AMP) levels were within control levels. On the other hand, the levels of ATP, ADP and AMP in the erythrocytes without mitochondria were not suppressed by the iron lactate overloading. Free activity of 3'-AMP forming enzyme, one of ribonucleases (RNase), was not changed in the liver of iron-overloaded rat, and total amount of 3'-AMP and adenosine formed after the treatment of the crude enzyme(s) with p-chloromercuribenzensulfonic acid, a SH blocker of RNase inhibitors, was decreased dose-dependently. On the contrary, free activity of 3'-AMP forming enzyme was enhanced dose-dependently in the spleen of iron-overloaded rat but the total activity was not changed. However, the free and total 3'-AMP forming enzyme activities in the liver and spleen of iron-overloaded rats became equal at the dosage of 5.0% of iron lactate. The results obtained suggested that iron loading might induce significant decrease in hepatic and splenic ATP levels via malfunction of their mitochondria and might lead dissociation of RNase-RNase inhibitor complex to activate 3'-AMP forming enzyme in both tissues.
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PMID:Effect of iron lactate overloading on adenine nucleotide levels and adenosine 3'-monophosphate forming enzyme in rat liver and spleen. 1534 Feb 21

IPC (ischaemic preconditioning) may protect the steatotic liver, which is particularly susceptible to I/R (ischaemia/reperfusion) injury. Hepatic steatosis was induced in Sprague-Dawley rats with a high-cholesterol (2%) diet for 12 weeks after which rats were subjected to I/R (ischaemia/reperfusion; 45 min of lobar ischaemia followed by 2 h of reperfusion). Rats were divided into three study groups (n=6 each) receiving: (i) sham laparotomy alone, (ii) I/R, and (iii) IPC (5 min of ischaemia, followed by 10 min of reperfusion) before I/R. Hepatic extra- and intra-cellular oxygenation and HM (hepatic microcirculation) were measured with near-infrared spectroscopy and laser Doppler flowmetry respectively. Plasma liver enzymes and hepatic tissue ATP were measured as markers of liver injury. Histology showed moderate-grade steatosis in the livers. At the end of 2 h of reperfusion, I/R significantly decreased extra- and intra-cellular oxygenation concomitant with a failure of recovery of HM (21.1+/-14.4% of baseline; P<0.001 compared with sham animals). IPC increased intracellular oxygenation (redox state of the copper centre of cytochrome oxidase; P<0.05 compared with rats receiving I/R alone) and flow in HM (70.9+/-17.1% of baseline; P<0.001 compared with rats receiving I/R alone). Hepatocellular injury was significantly reduced with IPC compared with I/R injury alone (alanine aminotransferase, 474.8+/-122.3 compared with 5436.3+/-984.7 units/l respectively; P<0.01; aspartate aminotransferase, 630.8+/-76.9 compared with 3166.3+/-379.6 units/l respectively; P<0.01]. In conclusion, IPC has a hepatoprotective effect against I/R injury in livers with moderate steatosis. These data may have important clinical implications in liver surgery and transplantation.
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PMID:Effect of ischaemic preconditioning on hepatic oxygenation, microcirculation and function in a rat model of moderate hepatic steatosis. 1534 10

Steatotic mice are particularly susceptible to hepatic ischemia/reperfusion injury compared with their lean littermates. We have previously demonstrated that livers of mice having a spontaneous mutation in the leptin gene (ob/ob), resulting in global obesity and liver steatosis, are ATP depleted, are endotoxin sensitive, and do not survive (I/R) injury. We hypothesize that administration of an anti-LPS monoclonal antibody (mAb) prior to initiation of I/R would be protective from that insult. Steatotic mice (ob/ob) were subjected to 15 min of ischemia via complete porta-hepatis occlusion and varying lengths of reperfusion with or without pre-treatment with an anti-LPS mAb. There was 14-31% survival of isotype matched control mAb treated ob/ob mice after 15 min of ischemia and 24 h of reperfusion. In contrast, 75-83% of ob/ob mice pre-treated with an anti-LPS mAb prior to initiation of I/R survived both ischemia and 24 h of reperfusion. Furthermore, there was a decrease in ALT and circulating endotoxin levels when treated with an anti-LPS mAb compared with control antibodies. Attenuation of the endotoxin load with anti-LPS mAb, prior to initiation of I/R, was cytoprotective and improved survival. Consequently, these studies might offer a solution to the problems associated with using steatotic livers in clinical transplantation.
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PMID:Anti-endotoxin monoclonal antibodies are protective against hepatic ischemia/reperfusion injury in steatotic mice. 1536 11

Fatty livers of obese fa/fa rats are vulnerable to injury when challenged by insults such as endotoxin, ischemia-reperfusion or acute ethanol treatment. The objective of this study was to evaluate whether a high-fat diet can act as a "second hit" and cause progression to liver injury in obese fa/fa rats compared with lean Fa/? rats. Accordingly, obese fa/fa rats and their lean littermates were fed a diet low in fat (12% of total calories) or a diet with 60% calories as lard for 8 weeks. Hyperglycemia and steatohepatitis occurred in the fa/fa rats fed the high-fat diet. This was accompanied by liver injury as assessed by alanine aminotransferase, hematoxilin and eosin staining, increased TNFalpha and stellate cell-derived TGFbeta, collagen deposition, and up-regulation of alpha-smooth muscle actin. Active MMP13 decreased in fa/fa rats independently of the diet, and TIMP1 expression increased with the high-fat diet, especially in fa/fa rats. Although UCP2 expression was higher in fa/fa rats regardless of the diet, minor changes in ATP levels were observed. Oxidative stress occurred in the fa/fa rats fed the high-fat diet as lipid peroxidation and protein carbonyls were elevated, while glutathione and antioxidant enzymes were very low. Expression and activity of cytochrome P450 2E1 and xanthine oxidase activity were down-regulated in fa/fa compared with Fa/? rats, and no effect was seen by the high-fat diet. However, NADPH oxidase activity increased 2.5-fold in fa/fa rats fed with the high-fat diet. In summary, a high-fat diet induces liver injury in fa/fa rats leading to periportal fibrosis. A role for oxidative stress is suggested via increased NADPH oxidase activity, lipid peroxidation, protein carbonyl formation, and low antioxidant defense.
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PMID:A high-fat diet leads to the progression of non-alcoholic fatty liver disease in obese rats. 1552 5

Fructose-1,6-bisphosphate (FBP) has been reported to have a protective effect on liver injury following ischemic/reperfusion periods because it maintains ATP levels during cold preservation. In the present study, we evaluated the effects of addition of FBP to storage solutions for cold liver preservation during 12 or 36 hours. Adult male Wistar rats were randomly divided into three experimental groups. The hepatic perfusion and preservation were performed with these solutions: UW; UW plus 10 mmol/L FBP; and FBP 10 mmol/L (FBPS) alone. The biochemical measurements of AST and ALT were performed on samples of the cold storage solution after 12- or 36-hour preservation. UW and FBPS solutions showed similar preservation grades at 12 hours. Addition of 10 mmol/L of FBP to UW solution induced liver injury and a poor preservation grade during 12 or 36 hours. UW solution was better than FBPS after 36 hours preservation. UW solution continues to offer a superior performance for liver preservation during long times; however, FBPS may be an alternative for short cold preservation times.
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PMID:Effect of fructose-1,6-bisphosphate in the cold storage solution after 12 and 36 hours of rat liver preservation. 1562 Oct 98

We tested the hypothesis that an acute decrease in muscle TCA cycle intermediates during contraction would compromise aerobic energy delivery. Male Wistar rats were anaesthetized and the gastrocnemius-plantaris-soleus (GPS) muscle complex from one leg was isolated and perfused with a red cell medium containing either saline (Con) or cycloserine (Cyclo; 0.05 mg g-1), an inhibitor of alanine aminotransferase (AAT). After 1 h of perfusion, the GPS muscle was either snap frozen (Con-Rest, n=11; Cyclo-Rest, n=9) or stimulated to contract for 10 min (1 Hz, 0.3 ms, 2 V) with blood flow fixed at 30 ml min-1 (100 g)-1 and then snap frozen (Con-Stim, n=10; Cyclo-Stim, n=10). Maximal AAT activity was>80% lower (P<0.001) in both Cyclo-treated groups (Rest: 0.61+/-0.02; Stim: 0.63+/-0.01 mmol (kg wet wt)-1 min-1; mean+/-s.e.m.) compared to Con (Rest: 3.56+/-0.16; Stim: 3.92+/-0.29). The sum of five measured TCAI (SigmaTCAI) was reduced by 23% in Cyclo-Rest versus Con-Rest but this was not different (P=0.08). However, after 10 min of contraction, the SigmaTCAI was 25% lower (P=0.006) in Cyclo-Stim compared to Con-Stim (1.88+/-0.15 versus 2.48+/-0.11 mmol (kg dry wt)-1). Despite the acute decrease in TCAI after Cyclo treatment, the contraction-induced changes in markers of non-oxidative energy provision (phosphocreatine, ATP and lactate) and the decline in tension after 10 min of stimulation were similar compared to Con. These data do not support the hypothesis that the total muscle concentration of TCAI is causally linked to the rate of mitochondrial respiration during contraction.
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PMID:An acute decrease in TCA cycle intermediates does not affect aerobic energy delivery in contracting rat skeletal muscle. 1580 96

Ischemia-reperfusion injury is responsible for the morbidity associated with liver surgery under total vascular exclusion or after liver transplantation. Recently, it has been reported that mitochondrial K(ATP) channel openers have an effect on myocardial protection via a pharmacological preconditioning action. However, it remains unclear as to whether K(ATP) channel openers can reduce ischemia-reperfusion injury in the liver. The aim of this study was to determine the effects of the mitochondrial K(ATP) channel opener, nicorandil, on ischemia-reperfusion injury in the rat liver. Male Wistar rats were subjected to 73% ischemia for 45 minutes followed by 120 minutes of reperfusion. Nicorandil (3 mg/kg) was orally administered 60 minutes before hepatic ischemia. Nicorandil significantly decreased plasma levels of alanine aminotransferase and lactate dehydrogenase by about 50% and inhibited the remarkably increased TUNEL-positive hepatocytes after reperfusion. Some mediators associated with apoptosis were analyzed by Western blotting. Cytochrome-c and caspase-3 levels in the cytosol increased after reperfusion; nicorandil inhibited the release of cytochrome-c and activation of caspase-3. The expression of Bax and Bcl-2 was significantly increased after reperfusion, being slightly inhibited by the administration of nicorandil. These results suggest that the protective effects of nicorandil against hepatic ischemia-reperfusion injury correlate with the inhibition of mitochondrial cytochrome-c release and caspase-3 activation. These findings demonstrate that nicorandil may become a therapeutic drug for ischemia reperfusion-related liver injury.
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PMID:Mitochondrial K(ATP) channel opener prevents ischemia-reperfusion injury in rat liver. 1580 66


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