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)

The inclusion of rats aboard Spacelab 3 (SL-3) allowed analyses of liver lipids, glycogen, hepatic enzymes of cholesterol, glycerolipid and sphingolipid biosynthesis, and other enzyme activities. Glycogen content was markedly elevated in livers from the flight animals compared with controls. Cholesterol was 24% (P less than 0.04) lower in livers from the experimental groups, whereas blood cholesterol was 19% higher (P less than 0.05). The activity of 3-hydroxy-3-methylglutaryl-CoA reductase, the rate-limiting enzyme of steroid biosynthesis, was 80% lower (P less than 0.01). Total phospholipids and sphingolipid levels did not differ significantly. The specific activity of fatty acyl-CoA synthetase, which is responsible for activation of fatty acids, was 37% (P less than 0.05) higher in microsomes from the rats on SL-3; however, since these animals had 25% less microsomal protein (P less than 0.02), there was no difference per gram of liver. The initial enzymes of sphingolipid and glycerolipid biosynthesis were assayed; serine palmitoyltransferase was 40% lower (P less than 0.01), and glycerol 3-phosphate acyltransferase did not differ. Hepatic cytochrome P-450 content decreased by 50% after spaceflight. Enzymes that did not differ significantly between the two groups include cytochrome b5, glutathione S-transferase, tyrosine aminotransferase, aspartate aminotransferase, and cystathionase. These findings suggest that spaceflight alters hepatic metabolism of several classes of compounds.
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PMID:Hepatic function in rats after spaceflight: effects on lipids, glycogen, and enzymes. 381 60

Myriocin, a fungal metabolite isolated from Myriococcum albomyces, Isaria sinclairi, and Mycelia sterilia, is a potent inhibitor of serine palmitoyltransferase (SPT), a key enzyme in de novo synthesis of sphingolipids. To evaluate the biological effects of myriocin in vivo, we investigated the levels of free sphingoid bases and expression of selected genes regulating cell growth in mouse liver. Male Balb/c mice, weighing 22 g were injected intraperitoneally with myriocin at 0, 0.1, 0.3, and 1.0 mg kg(-1) body weight daily for 5 days. Animals were euthanized 24 hours after the last treatment. Levels of plasma alanine aminotransferase and aspartate aminotransferase were not significantly altered by the treatment. A dose-dependent decrease in free sphinganine but not sphingosine was detected by high performance liquid chromatography in both liver and kidney. The decrease of free sphinganine paralleled the decrease in SPT activity. Reverse transcriptase polymerase chain reaction analysis on liver mRNA revealed an increase in expression of c-myc, but no changes in tumor necrosis factor alpha, transforming growth factor beta, and hepatocyte growth factor. Results showed that myriocin blocked de novo synthesis of sphingolipids in vivo by SPT inhibition and induced c-myc expression in liver.
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PMID:Inhibition of serine palmitoyltransferase by myriocin, a natural mycotoxin, causes induction of c-myc in mouse liver. 1518 Jan 63

Fumonisin B(1) (FB(1)), a mycotoxin produced by Fusarium verticillioides present on corn and corn-based products, causes species- and organ-specific diseases. The hepatotoxic effects of FB(1) in mice have been closely correlated with the accumulation of free sphinganine, a marker for ceramide synthase inhibition, and reduced biosynthesis of more complex sphingolipids. It has been shown that FB(1) modulates expression of many cell signaling factors. In the current study we used myriocin, a specific inhibitor of serine palmitoyltransferase, to investigate the role of free sphinganine accumulation in FB(1)-induced hepatotoxicity and increased expression of selected signaling genes in BALB/c mice. The mice were pretreated daily with intraperitoneal injection of 1.0 mg/kg myriocin 30 min before subcutaneous injections of 2.25 mg/kg of FB(1) for 3 days. Results showed that myriocin alone was not hepatotoxic and the combination of myriocin plus FB(1) completely prevented the FB(1)-induced elevation of hepatic free sphinganine and prevented the FB(1)-induced induction of selected cell signaling genes, suggesting that accumulation of free sphinganine and/or its metabolites contribute to the FB(1)-modulation of the cell signaling factors. However, the combination of myriocin and FB(1) did not prevent FB(1)-increased concentration of plasma alanine aminotransferase and only slightly attenuated aspartate aminotransferase; it did not affect the FB(1)-induced hepatocyte apoptosis or increased cell proliferation. A longer combined treatment of myriocin and FB(1) was highly toxic. The hepatotoxic effects in mice seen in this study are most likely due to a combination of factors including accumulation of free sphinganine, depletion of more complex sphingolipids and sphingomyelin, or other unknown mechanisms.
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PMID:Myriocin prevents fumonisin B1-induced sphingoid base accumulation in mice liver without ameliorating hepatotoxicity. 1581 77