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)

Cytoplasmic proteins are degraded with different half-lives in vivo. Large parts of proteins are believed to be degraded primarily in autophagic vacuoles-lysosomal system. However, the mechanism by which cell proteins are delivered to lysosomes and whether such a process might be selective for certain cell proteins are still unresolved. We examined the mechanism of autophagy with isolated autophagic vacuoles. Administration of leupeptin, a inhibitor of lysosomal thiol proteinases, induced the accumulation of numerous autophagic vacuoles in the liver. Highly purified preparation of autophagic vacuoles was isolated by Percoll density gradient equilibrium fractionation of crude lysosomal fractions. When cytosolic enzyme activities in autophagic vacuoles were measured, tyrosine aminotransferase and tryptophan oxygenase with short half-lives, and lactic dehydrogenase and aspartate aminotransferase with long half-lives were detected at similar ratios of enzymes in autophagic vacuoles/cytosol. During the time that cathepsin B plus L activities in autophagic vacuoles are inhibited by the injection of leupeptin, cytosolic enzymes are being accumulated in autophagic vacuoles suggesting that leupeptin blocks intralysosomal proteolysis, and that cytosolic enzymes are sequestered continuously into autophagosomes. Administration of glucocorticoid, which induces the synthesis of tyrosine aminotransferase, tryptophan oxygenase and cytosolic aspartate aminotransferase, selectively increased the sequestration of these enzymes to proportional degrees. Dietary manipulation and administration of insulin, which inhibit the formation of autophagic vacuoles, suppressed completely the accumulation of autophagic vacuoles in liver by administration of leupeptin. Results indicate that there is no selective uptake of cytosolic enzymes into autophagosome. When distribution of lysosomal cathepsin B and L in liver, which are inhibited strongly by leupeptin, was examined immunohistochemically, cathepsin L is found only in hepatocytes, but cathepsin B is localized in sinusoidal cells rather than in hepatocytes, suggesting that cathepsin L plays a most important role in intralysosomal proteolysis in hepatocytes.
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PMID:Lysosomal sequestration of cytosolic enzymes and lysosomal thiol cathepsins. 390 2

Most acute respiratory distress syndrome studies have been focused on the lung injury. Little is known about other organs during the development of acute respiratory distress syndrome. Herein, we investigated the injury and cell death in multiple organs after intestinal ischemia-reperfusion (IIR) in C57BL/6 mice. Terminal transferase dUTP nick end labeling staining was used as a marker of cell death. Caspase 3 and cathepsin B activation as markers of caspase-dependent and caspase-independent apoptosis, respectively, and electron microscopy for ultimate characterization of cell death were used. In comparison with control and sham-operated mice, the IIR group showed interstitial inflammatory infiltrates in the lung and significant increases of lung injury parameters and plasma lactate dehydrogenase and aspartate aminotransferase levels. Terminal transferase dUTP nick end labeling-positive cells and immunostaining for hemeoxygenase 1, an enzyme induced by inflammatory stimuli, were increased in the lung, heart, and kidney, but not in the liver. The number of hemeoxygenase 1-positive cells positively and significantly correlated to the number of terminal transferase dUTP nick end labeling-positive cells. Cell death was not associated with caspase 3 or cathepsin B activation. Electron microscopy showed morphological features compatible with oncotic rather than apoptotic cell death or necrosis, including mitochondrial swelling and cytoplasm disorganization in pulmonary and renal epithelial cells, lung and cardiac endothelial cells, and myocytes. These results indicate that, although lung injury is the most significant manifestation after IIR, oncotic cell death occurs in the lung, heart, and kidney, which may be related to ischemia and inflammation.
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PMID:Intestinal ischemia-reperfusion-induced acute lung injury and oncotic cell death in multiple organs. 1766 44

The aim of this paper was to assess the influence of Fasciola hepatica infection on oxidative modifications of rat liver cell components such as proteins and lipids. Wistar rats were infected per os with 30 metacercariae of F. hepatica. Activities and concentrations of liver damage markers were determined in the 4th, 7th, and 10th week postinfection (wpi). A decrease in antioxidant capacity of the host liver, manifested by a decrease in total antioxidant status (TAS), was observed. Diminution of antioxidant abilities resulted in enhanced oxidative modifications of lipids and proteins. F. hepatica infection enhanced lipid peroxidation, which was visible in the statistically significant increase in the level of different lipid peroxidation products such as conjugated dienes (CDs), lipid hydroperoxides (LOOHs), malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE). The level of protein modification markers in the rat liver was also significantly changed and the most intensified changes were observed at seventh week postinfection. Concentration of carbonyl groups and dityrosine was significantly increased, whereas the level of tryptophan and sulfhydryl and amino groups was decreased. Changes in the antioxidant abilities of the liver and in the lipid and protein structure of the cell components resulted in destruction of the function of the liver. F. hepatica infection was accompanied by raising serum activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) as markers of liver damage. A significant decrease in lysosomal as well as in the total activity of cathepsin B during fasciolosis was also observed.
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PMID:Oxidative Modifications of Rat Liver Cell Components During Fasciola hepatica Infection. 1969 38