Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rats were given ethanol chronically (20-30% of the energy) in a nutritionally sufficient diet regimen. Controls received lipid as an isoenergetic substitute for ethanol. Protein synthesis in hepatocytes isolated from ethanol-fed rats was decreased compared with controls, but not in isolated nonparenchymal liver cells. Ethanol added in vitro inhibited protein synthesis in hepatocytes by 30%, but not in nonparenchymal cells for both ethanol-fed and control rats. Protein export and protein degradation in isolated hepatocytes were not affected by long-term ethanol treatment. Isolated hepatocytes were separated according to their buoyant density in linear metrizamide gradients. They were distributed in a bell-shaped manner regardless of donor rat treatment. Cells of low density contained three times as much lipid as high density cells. They were probably enriched in periportal cells, since histologic examination indicated a predominantly periportal localization of cells containing lipid droplets. Distribution of the intra-acinar marker alanine aminotransferase supported this conclusion. Protein synthesis was similar in the low-density hepatocyte populations of the respective groups of rats, whereas it was inhibited in a high-density population of ethanol-treated rats compared to the controls. Inhibition of protein synthesis by 80 mM ethanol was lower in the low-density hepatocytes of ethanol-fed rats.
Exp Mol Pathol 1984 Aug
PMID:Ethanol effects on protein synthesis in nonparenchymal liver cells, hepatocytes, and density populations of hepatocytes. 646 35

The usefulness of measuring serum-conjugated bile acid concentrations by radioimmunoassay in colchicine-modified carbon tetrachloride-induced liver lesions in rats was assessed by comparing the concentrations with the results of some routinely employed liver function tests such as serum aspartate transaminase, alanine transaminase, alkaline phosphatase, and serum total protein. The serum cholylglycine levels were significantly (P less than 0.003) raised along with the serum aspartate transaminase (P less than 0.01) and alanine transaminase (P less than 0.01) activity levels in the carbon tetrachloride-treated group of rats when compared with the group treated with carbon tetrachloride plus colchicine. Colchicine prevented the increase in serum cholylglycine, aspartate transaminase, alanine transaminase, and alkaline phosphatase induced by carbon tetrachloride but had no effect on serum total protein levels. This study suggests that radioimmunoassay of serum cholyglycine is a sensitive and specific indicator of liver injury and it is a useful tool in monitoring the treatment provided.
Exp Mol Pathol 1984 Dec
PMID:Serum bile acid in the evaluation of colchicine treatment of carbon tetrachloride-induced liver injury. 651 May 12

In the adipose tissue, besides fatty acid synthesis (FA-S) from glucose, which includes several mitochondrial steps, FA-S from glutamate has been demonstrated. FA-S from glutamate takes place in the cytosol through the backward pathway of Krebs cycle (BPKC) and is due to the sequential action of (1) alanine aminotransferase (ALT, EC 2.6.1.2), which is presence of pyruvate converts glutamate to oxoglutarate; (2) isocitrate dehydrogenase (NADP) (ICDH, EC 1.1.1.42), which converts oxoglutarate to isocitrate; (3) aconitate hydratase (ACO, EC 4.2.1.3), which transforms isocitrate to citrate: and (4) ATP citrate-lyase (ATP-CL, EC 4.1.3.8), which splits citrate to yield the acetyl-CoA needed for FA-S. We studied the enzymes involved in BPKC in homogenates of human adipose tissue. In normal subjects, the cytosolic activity (mumol/min/g protein) was: ALT = 10.3 +/- 1.1, ICDH = 29.5 +/- 2.8, ACO = 2.05 +/- 0.23, and ATP-CL = 1.2 +/- 0.2. Mitochondria contained less or no activity, values being 20, 9, 11, and 0% of total for ATL, ICDH, ACO, and ATP-CL, respectively. BPKC enzymes are more active than the enzymes limiting FA-S from glucose, i.e., phosphofructokinase (EC 2.7.1.11), pyruvate carboxylase (EC 6.4.1.1), and pyruvate dehydrogenase (EC 1.2.4.1). In the obese patients, cytosolic ALT and ATP-CL were increased (12.9 +/- 0.7, P < 0.05, and 2.28 +/- 0.27, P < 0.01, respectively) compared to normal, while ICDH was not changed (ACO could not be studied). Similar changes were obtained by expressing enzyme activity per fat cell number.(ABSTRACT TRUNCATED AT 250 WORDS)
Biochem Mol Med 1995 Feb
PMID:Fatty acid synthesis from glutamate in the adipose tissue of normal subjects and obese patients: an enzyme study. 755 12

Erythrocyte aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities are often used as indices of vitamin B-6 nutritional status; however, results using a mixed population of erythrocytes can be quite variable. Erythrocytes from two strains of mice (Mus domesticus), A/Ibg and DBA/Ibg, were separated according to age by centrifugation through discontinuous Percoll density gradients into three fractions: top (least dense, youngest), middle and bottom (most dense, oldest). A sufficient yield of age-fractionated erythrocytes was obtained from a single mouse for all of the enzyme measurements. The activities of AST, ALT and three age-marker enzymes, pyruvate kinase, acetylcholinesterase and hexokinase, were found to be significantly higher in the youngest cell fractions, and declined in the older, more dense fractions. A mice had significantly lower AST and ALT activities in the age separated fractions than did DBA mice. The measurement of enzyme activities in low density, young cells may be especially useful in studies involving conditions in which the proportion of young erythrocytes may be elevated with respect to the entire erythrocyte mass.
Comp Biochem Physiol B Biochem Mol Biol
PMID:Aminotransferase activities in mouse, Mus domesticus, erythrocytes separated according to age. 755 57

Intravenous administration of a single dose (100 micrograms/kg bw) of recombinant tumour necrosis factor-alpha (TNF, cachectin) to rats increased the rate of in vitro fatty acid synthesis in interscapular brown adipose tissue (IBAT) from both glucose and alanine, without changes in the oxidation of these substrates to 14CO2. Lactate production and glycerol release were also unaffected by treatment with the cytokine. Additionally, the presence of TNF in the incubation media did not affect fatty acid synthesis, suggesting an indirect effect of the cytokine. The activities of different enzymes of glucose and alanine metabolism such as hexokinase, phosphofructokinase, pyruvate kinase, glucose-6-phosphate dehydrogenase and alanine transaminase, did not suffer changes as a consequence of TNF administration. The same applied to the enzymatic activities involved in fatty acid synthesis such as fatty acid synthase, acetyl-CoA carboxylase and ATP-citrate lyase. Conversely, citrate levels in IBAT were increased in animals treated with TNF, suggesting that it could be the cause for the increased fatty acid synthesis in this tissue.
Mol Cell Biochem 1995 Feb 23
PMID:Metabolic effects of tumour necrosis factor-alpha on rat brown adipose tissue. 759 46

Nicotinic acetylcholine receptors (nAChRs), like other calcium permeable channel receptors, may play a crucial role during neuronal development. We have characterized nAChRs in developing mouse cerebellar granule cells in primary culture. L-[3H]Nicotine, [3H]cytisine and [125I]alpha-bungarotoxin binding experiments revealed the presence of a single class of saturable and specific high affinity binding sites for each ligand. The expression of these nicotinic binding sites followed a developmental pattern reaching a maximum during the establishment of excitatory amino acid synaptic contacts. Immunolabeling with monoclonal antibodies to nAChR subunits revealed the presence of alpha 4 and beta 2 subunits in most neurons. Moreover, some neuronal cells displayed a somatic as well as a neuritic localization for the alpha 7 subunit as shown by [125I]alpha-bungarotoxin autoradiography. The reverse transcription-polymerase chain reaction (RT-PCR) detected the presence of mRNAs for alpha 3, alpha 4, alpha 5, alpha 7, beta 2 and beta 4 nAChR subunits. Non-neuronal cells did not express nAChRs, as shown by [3H]nicotine and [125I]alpha-bungarotoxin binding, immunocytochemistry and PCR. Maximum Ca2+ influx elicited by nicotine, and partly sensitive to alpha-bungarotoxin, was observed around 10-14 days after plating. This correlated with the time period at which the highest number of nicotine binding sites was detected. Sensitivity to several NMDA receptor antagonists as well as to removal of endogenous glutamate by pyruvate transaminase treatment revealed a glutamatergic component in the nicotine stimulated calcium influx. The time-dependent specific nAChR expression and the potential association between nAChRs and NMDA receptor activation suggest that nAChRs may regulate glutamatergic activity during synaptogenesis in cerebellar granule cells.
Brain Res Mol Brain Res 1995 May
PMID:Characterization of nicotinic acetylcholine receptors expressed in primary cultures of cerebellar granule cells. 760 40

The p53 tumor-suppressor gene is the most commonly altered gene in human cancers. Here we demonstrate that transcripts of the mdm2 gene, which encodes a cellular p53 binding protein, markedly increased in the rat liver within 1 to 3 h, reached a peak at 12 h and returned to the basal level 48 h after the administration of carbon tetrachloride. However, the level of hepatic mdm2 mRNA did not significantly change after partial hepatectomy. This is in contrast to p53 gene expression which increased after either procedure. C-myc transcripts also rapidly increased after the injection of carbon tetrachloride, reaching a maximal level at 3 h. The activity of serum alanine aminotransferase was low within the first 12 h and was maximal 24 h after carbon tetrachloride. These results suggest that the transient hepatic expression of the mdm2 gene prior to the onset of cell death is more likely to reflect events associated with necrosis rather than with cell proliferation.
Biochem Mol Biol Int 1995 Jun
PMID:Expression of the protooncogene mdm2 markedly increases in response to carbon tetrachloride but not after partial hepatectomy in contrast to p53. 766 43

In mice depleted of glutathione (GSH) by pretreatment with an inhibitor of GSH synthesis, buthionine sulfoximine (BSO; 1 hr before styrene, 2 mmol/kg or higher doses, ip), styrene (0.96-5.76 mmol/kg, po) produced hepatotoxicity characterized by an increase in serum alanine transaminase activity and cetrilobular necrosis of hepatocytes. Treatment with inhibitors of hepatic cytochrome P-450-dependent monooxygenases such as carbon disulfide, methoxsalen, piperonyl butoxide, and SKF-525A prevented or tended to reduce the hepatotoxic effect of styrene given in combination with BSO. Styrene 7,8-oxide (3.84 mmol/kg, po), a known metabolite of styrene, in combination with BSO caused an earlier and larger increase in SALT than that caused by an equimolar dose of styrene in combination with BSO. These results suggest that metabolism of styrene, possibly to styrene 7,8-oxide, is a necessary step in styrene-induced hepatotoxicity in GSH-depleted mice. Before the onset of hepatotoxicity, styrene in combination with BSO produced a larger and more prolonged depletion of hepatic GSH than that seen after the sole treatment with BSO or prolonged depletion of hepatic GSH than that seen after the sole treatment with BSO or styrene, but no depletion of hepatic protein sulfhydryls was induced by styrene in combination with BSO.
Res Commun Mol Pathol Pharmacol 1994 Dec
PMID:Styrene-induced hepatotoxicity in mice depleted of glutathione. 771 12

The mitochondrial FAD-linked enzyme glycerophosphate dehydrogenase plays a key role in the pancreatic B-cell glucose sensing device. In the present study, the activity of this enzyme was examined in islets of fa/fa rats in which inherited diabetes mellitus is associated with obesity, hyperinsulinism and severe insulin resistance. The specific activity of both FAD-linked glycerophosphate dehydrogenase and glutamate dehydrogenase were decreased in islet and liver homogenates prepared from fa/fa, as compared to Fa/Fa, rats, this coinciding with a low ratio between glutamateoxalacetate and glutamate-pyruvate transaminase activity in both islet and liver extracts, islet hyperplasia, hyperinsulinemia and hepatic steatosis in the hyperglycemic fa/fa rats. It is speculated that a low activity of FAD-linked glycerophosphate dehydrogenase in the pancreatic B-cell may participate to the perturbation of glucose homeostasis in fa/fa rats, like in other animal models of non-insulin-dependent diabetes mellitus.
Mol Cell Biochem 1994 Jun 29
PMID:Impaired FAD-glycerophosphate dehydrogenase activity in islet and liver homogenates of fa/fa rats. 783 41

Whether calcium-binding protein regucalcin, which mainly localizes in liver, is released into the serum by liver injury was investigated in rats administered galactosamine. Galactosamine (25 mg/100 g body weight) was intraperitoneally administered 3 times at 2 h intervals in rats, and the animals were sacrificed at 10, 24 and 48 h after the first administration of galactosamine. Liver regucalcin mRNA levels were clearly reduced at 24 and 48 h after galactosamine administration with estimating for Northern blotting assay. When hepatic regucalcin concentration was estimated by enzyme-linked immunoadsorbent assay (ELISA) with rabbit-anti-regucalcin IgG, liver regucalcin concentration was not significantly altered by galactosamine administration. Serum regucalcin concentration was markedly elevated at 10 and 24 h after the first administration of galactosamine. Serum transaminases (GOT and GPT) activities were significantly increased by galactosamine administration, indicating that liver injury was induced. The present study demonstrates that liver regucalcin is released into the serum by liver injury with galactosamine administration in rats.
Mol Cell Biochem 1994 Jul 13
PMID:Serum release of hepatic calcium-binding protein regucalcin by liver injury with galactosamine administration in rats. 785 35


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