[Schizophrenia and the corpus callosum: morphologic and functional approach].
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Adolescent↗
Biomedical subjects
F Antoni
Publications and source records attributed to F Antoni.
Endotoxin inhibits glucuronidation in the liver. An effect mediated by intercellular communication.
Endotoxin [lipopolysaccharide (LPS) 50 micrograms/mL] added to the perfusion medium increased glucose production and inhibited the glucuronidation of p-nitrophenol in perfused mouse liver both in recirculating and non-recirculating systems, while sulfation of p-nitrophenol was unchanged. The effects of endotoxin could be prevented by the addition of cyclooxygenase inhibitors, while PGD2 and PGE2 also caused a decrease in p-nitrophenol glucuronidation in perfused liver. In isolated hepatocytes endotoxin failed to affect p-nitrophenol conjugation, while PGD2 and PGE2 decreased the rate of it. Our results suggest that endotoxin inhibits glucuronidation through an intercellular communication presumably mediated by eicosanoids.
Animals↗
Net glucose production from acetone in isolated murine hepatocytes. The effect of different pretreatments of mice.
1. To evaluate the condition under which net glucose production from acetone, added as sole substrate, occurs different pretreatments of mice, in combination with starvation, were used; (i) acetone pretreatment (acetone is a known inducer of cytochrome P-450 isozymes involved in this pathway), (ii) fructose pretreatment (to induce NADPH+H+ generating enzymes) or (iii) their combination. 2. There was net glucose formation from acetone only in that case, when the cells were prepared from 48 hr fasted animals pretreated with both acetone and fructose. However, using 2-14C-acetone, incorporation of 14C-carbon into glucose could be detected in all the cases and, at the same time, acetone was without any effect on protein synthesis. 3. The addition of acetone increased gluconeogenesis from alanine in almost all the cases. The only exception from this general rule was that the case, when hepatocytes were prepared from acetone pretreated 48 hr starved mice where, instead of the elevation of glucose formation, a decrease of that was caused by acetone. 4. Acetone decreased 14C-carbon incorporation into glucose from 14C-(U)-alanine added at saturating concentration in hepatocytes prepared from starved mice. 5. Similarly to acetone there was no net glucose formation from acetone either when added alone, however, it enhanced gluconeogenesis from alanine at non-saturating concentrations of the amino acid. 6. Methylglyoxal proved gluconeogenic in all the cases. 7. It is concluded that net glucose formation from acetone as sole substrate occurs only under those conditions which are far from a physiological situation, however, when gluconeogenesis from another substrate takes place, acetone can contribute to net glucose formation in hepatocytes prepared from fasted mice.
Acetone↗
Formation of leucyl-leucine-O-methylester in leucine-O-methylester treated cells.
Porcine polymorphonuclear cells (PMN) and murine macrophages (M phi) were treated in vitro with Leu-OMe or Leu-Leu-OMe (1.5-5.0 mM) for various periods of time. It was found that the Leu-OMe and Leu-Leu-OMe entered cells rapidly, concomitantly the intracellular leucine accumulated. The methyl derivative diffused faster than Leucine due to its lipophylic character. The Leucine-O-methylesters hydrolysed rapidly as a consequence of the esterase and peptidase activities. The cells treated with Leu-OMe accumulated a high amount of Leucine and some Leu-Leu-OMe too. It was found that the formation of the didpeptide-methylester is not a spontaneous process, rather an enzymatic one. The Leu-OMe treated cells serve as a model which can be used to investigate the effect of the amino acid metabolism and the formation of dipeptides intracellularly and extracellularly.
Animals↗
In vitro effect of leucine-O-methylester on polymorphonuclear and mononuclear cells.
The uptake of Leu-OMe and Leu-Leu-OMe was studied in vitro in porcine PMN cells. Both methylesters are metabolized leading to the intracellular accumulation of leucine. Part of the hydrolyzed leucine gradually filtrates back into the culture medium in a time-, temperature- and methylester substrate concentration-dependent manner. Another portion of Leu-OMe is converted to Leu-Leu dipeptide. With respect to the cellular effects of Leu-OMe treatment ultrastructural studies showed the presence of large vacuoles without significant alteration of cell viability. Increased exocytosis of lysosomal enzymes did not lead to lytic events. Changes in the plasma membrane are indicated by the observation that Leu-OMe treatment causes the loss of the chemotactic activity to formyl-Met-Leu-Phe.
Animals↗
Evidence for the pre-synthesized state of secreted macrophage arginase: arginase activity cannot be modified in short-term cultures.
The arginase produced by peritoneal macrophages is not synthesized de novo in short-term (3 h) cultures after harvesting the cells. In long-term cultures the arginase synthesis is restored. In contrast to arginase lysozyme is continuously synthesized in short-term cultures. These statements were proved by the following experimental results: 1. Protein synthesis inhibitor and lysosomotropic agents did not alter the arginase level. 2. Arginine and its analogue, canavanine and ornithine were not able to change the arginase activity. 3. The product of an alternative metabolic pathway of arginine, sodium nitrite, did not affect arginase activity. 4. Effectors influencing the synthesis of cyclic nucleotides (cAMP, cGMP), indomethacin, sodium nitroprusside and an analogue of cAMP had no effect on the arginase activity. 5. Arginase activity could not be significantly modified either by an in vitro Micrococcus luteus treatment or by changing the adherence period of peritoneal exudate cells. 6. When arginase was produced in murine peritoneal macrophages at various periods with medium change, the total arginase released into the media from murine and rat macrophages did not exceed the original intracellular arginase content of the adhered cells during the first 6 hours.
Animals↗
Accumulation of S-D-lactoylglutathione and transient decrease of glutathione level caused by methylglyoxal load in isolated hepatocytes.
Methylglyoxal is converted to D-lactic acid through a conjugation with glutathione and S-D-lactoylglutathione is an intermediate of this pathway. In isolated hepatocytes prepared from fed mice incubated without nutrients (glucose, pyruvate and amino acids) the formation and release of S-D-lactoylglutathione and also a continuous lowering of cellular glutathione were demonstrated upon addition of methylglyoxal (20 mM). Under these incubation conditions, the glutathione content of the cells decreased in the controls. On the other hand, in hepatocytes incubated in a medium supplemented with the above-mentioned compounds an accumulation of S-D-lactoylglutathione and a transient decrease of glutathione were shown after addition of methylglyoxal. Under these experimental circumstances the glutathione content of the cells was preserved. Buthionine sulfoximine--an inhibitor of glutathione synthesis--prevented the restoration of glutathione level in hepatocytes observed in the presence of methylglyoxal; emetine--an inhibitor of protein synthesis--was ineffective. It is suggested that increased methylglyoxal formation may have a role in alterations of glutathione metabolism under conditions when serum acetone is increased and methylglyoxal production from acetone is elevated.
Acetone↗
[The effect of low density lipoprotein (LDL) on NO formation and on arginase activity in mouse peritoneal macrophages].
A large body of the evidence is available to the causative relationship between the elevated blood plasma concentrations of LDL and the atherogenesis. The oxid-LDL (modified LDL) is internalized more rapidly by the macrophages, and there is now substantial evidence that the modified LDL is actually present in atherosclerotic lesions. Recently it has been proved that the endothel cells and monocyta/macrophages generate nitric oxide (NO) from arginine, and that the LDL inhibits the formation of NO in endothel cells. The authors found that the human LDL in vitro exerts an inhibitory effect on the formation of NO in murine PED (peritoneal exudate cells) and synchronously severalfold increasing of the arginase activity in the culture media. Both effects of LDL proved to be dose dependent and the oxid-LDL has been found to be more effective. The increased activity of arginase provides a very likely explanation for the reducing of NO production in macrophage treated by LDL. The reducing or blocking of NO-formation causes a local vasocontraction which induces clinical symptoms.
Animals↗
[The role of endogenous free radicals of nitric oxide (NO)].
The role of endothelium in vasodilatation has only emerged in the last ten years. It was observed that many endogenous substances from endothelial cells triggered the release of a substance which was named endothelium-derived relaxing factor (EDRF). Later has been showed that NO accounted for most if not all of the biological activity of EDRF. The endothelial synthesis of NO originates from L-arginine and could be blocked by the methyl analogue (e.g. NG-mono-methyl-L-arginine). Beside endothelial cells NO could be identified in several mammalian tissues including brain, hepatocytes, lung and macrophages. NO mediated the control of vascular tone and blood pressure via vascular smooth muscle cells which exert relaxation and constriction of blood vessels. It is considered NO represents signal for the guanylate cyclase system which regulates the intracellular concentration of Ca2+ ions. It is well known that the concentration of Ca2+ ions play discern direct role in the relaxation and contraction of smooth muscle, respectively.
Endothelium↗
The effect of A23187 on glucose production from methylglyoxal and pyruvate in isolated murine hepatocytes.
1. A23187 increased the glucose production from methylglyoxal in isolated hepatocytes, and maximal stimulation was obtained at 10(-6) M. The effect of A23187 was dependent on the presence of Ca2+. 2. Glucose production from pyruvate (less than 1 mM) in isolated hepatocytes was stimulated by A23187 in the presence of 2.5 mM Ca2+ and was depressed at pyruvate concentrations above 1 mM. Both the virtual Km and the virtual Vmax of glucose production from pyruvate were decreased by A23187.
Animals↗
Inhibition of gluconeogenesis, ureogenesis and drug oxidation by redox cycler quinone in isolated mouse hepatocytes.
1. The effect of a redox cycler and arylator (menadione) and a pure arylator quinone (benzoquinone) was studied on different NADPH generating and consuming processes in isolated mouse hepatocytes. 2. Menadione inhibited gluconeogenesis from alanine but not from fructose or glycerol. 3. Drug oxidation measured as aniline hydroxylation and aminopyrine N-demethylation could be inhibited by menadione in microsomal membrane and in isolated hepatocytes both from fed or fasted animals. 4. Ureogenesis in isolated hepatocytes from fed mice could not be inhibited even by high concentration of menadione, while in cells from fasted animals menadione was inhibitory at high concentration in the presence of gluconeogenic precursor and at lower concentration in the absence of it. 5. Benzoquinone did not inhibit the above mentioned processes.
Aniline Hydroxylase↗
Inverse relation in the de novo arginase synthesis and nitric oxide production in murine and rat peritoneal macrophages in long-term cultures in vitro.
1. The de novo synthesis of arginase was much higher in murine than in rat peritoneal macrophages. This process was inhibited irreversibly by protein synthesis inhibitors and reversibly by glycolysis blockers. 2. Rat macrophages produce more nitric oxide (NO) than murine cells. NO production was inhibited by the inhibitors of protein synthesis or glycolysis. 3. The loading of macrophages by exogenous arginine for 24 hr in vitro resulted in the increase of arginase and nitrite in macrophages to different extents. 4. No great differences in lysozyme production was observed. 5. The proportion of arginine taken up and incorporated is contrasted in murine and rat macrophages.
Amino Acids↗
Differences and similarities in the sensitivity of lymphocytic and macrophage plasma membrane to deoxycholate.
Human tonsillar lymphocytes separated on nylon wool and rat macrophages showed different sensitivity to deoxycholate (DOC) treatment at a low (0.24 mM, 0.01%) concentration for 3 h. The T cell-enriched fraction was stimulated more readily by PHA whereas the B-cell enriched fraction lost its adherence and a decrease of chromium binding capacity was observed after the detergent treatment. Rat peritoneal macrophages under the same conditions lost their chromium label and lysozyme content, whereas their adherence and phagocytic capacity decreased dramatically without affecting their binding capacity. Higher sensitivity to the detergent was observed in peritoneal macrophages compared to tonsillar lymphocytes when various DOC concentrations were used. These findings proved that this low concentration DOC treatment, at least in macrophages, touched mainly the adhesive proteins and the dynamics of the membrane and not its receptor-associated properties.
Animals↗
High amounts of glucose and insulin inhibit p-nitrophenol conjugation in mouse hepatocytes.
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Animals↗
Effect of methylglyoxal on glucose formation, drug oxidation and glutathione content in isolated murine hepatocytes.
The first stage in the formation of glucose from acetone involves two oxidation steps catalyzed by isozymes of the cytochrome P-450 II E1 gene subfamily; methylglyoxal formed this way is further converted to pyruvate by a reversible conjugation with reduced glutathione. The effect of methylglyoxal on glucose formation, oxidation of aminopyrine, aniline and on reduced glutathione content was investigated in isolated hepatocytes prepared from (i) fasted or (ii) fasted and acetone (known to induce isozymes of P-450 II E1 gene subfamily) pretreated mice. Glucose formation and drug oxidation were increased by methylglyoxal at concentrations below 1 mM, but were severely decreased above 1 mM. Methylglyoxal also decreased protein synthesis at concentrations above 1 mM. If the addition of methylglyoxal was combined with that of other gluconeogenic precursors and glucose the initial increasing effect on drug oxidation was moderated or diminished and the decreasing effect (at high concentrations) was enhanced. The glutathione content of the cells was decreased by methylglyoxal in a concentration dependent manner. Acetone pretreatment of mice also resulted in a decreased glutathione content of the liver. Based on these observations it is assumed that methylglyoxal has contrasting effects in hepatocytes, and can contribute to the disturbed metabolism under circumstances when the acetone production is elevated.
Acetone↗
The 38 kDa Ca2+/membrane-binding protein of pig granulocytes needs a high Ca2+ concentration to be phosphorylated by protein kinase C.
The 38 kDa Ca2+/membrane-binding protein reported to be the dominant substrate of protein kinase C in the extracts of pig neutrophil granulocytes was purified partially and its phosphorylation was investigated. In pig granulocytes type II protein kinase C was the major isoform, while type III isoenzyme was present only as a minor activity. Phosphorylation of the 38 kDa protein was performed with rat brain protein kinase C. Each of the three isoenzymes purified from rat brain was able to phosphorylate this protein, though on the conditions used in our experiments it was phosphorylated most intensively by type II protein kinase C. A phospholipid-dependent, but Ca2(+)-independent, form of protein kinase C was demonstrated with the aid of a synthetic oligopeptide substrate. Phosphorylation of the 38 kDa protein by the Ca2(+)-independent enzyme proceeded exclusively in the presence of Ca2+. The Ca2+ concentration necessary for the phosphorylation of the 38 kDa by either form of protein kinase C was by orders of magnitude higher than that required for the activation of protein kinase C.
Amino Acid Sequence↗
Cytometric analysis of DNA replication inhibited by emetine and cyclosporin A.
DNA staining methods based on aspecific interactions with dye molecules have been replaced by an immunofluorescent approach to measure DNA replication. Biotin-11-dUTP was incorporated into permeable thymocytes isolated after emetine or cyclosporin A treatment of mice. Active sites of DNA replication were amplified based on biotin-avidin interaction and verified under fluorescent microscope. Cytometry of fluorescent images allow the direct measurement of replicating DNA without aspecific detection of total cellular DNA. Cytometric analysis of replication revealed that emetine acts at the early S phase, while cyclosporin A blocks in vivo DNA synthesis at mid S phase.
Animals↗
Differences in the arginase activity produced by resident and stimulated murine and rat peritoneal macrophages.
1. Murine macrophages showed a considerably higher in vitro arginase production in short time cultures than rat peritoneal cells. 2. The in vivo stimulation with casein or thioglycollate resulted in an enhanced in vitro enzyme production in mice. 3. The adherence is not the condition of the enzyme production. 4. The difference between the two species cannot be explained by the lack of bivalent ions, the absence of energy supply, proteolysis, the low number of macrophages or by the different cell types of the peritoneal exudate of mouse and rat. 5. The lysozyme production of murine and rat peritoneal macrophages was also investigated and no difference was observed between the two species.
Animals↗