PubMed Health⌕ Search

Biomedical subjects

D Cottalasso

Publications and source records attributed to D Cottalasso.

At least 19 recordsLinked to original sources
PubMed1990

Inactivation of hepatocyte protein kinase C by carbon tetrachloride: involvement of drug's metabolic activation and prooxidant effect.

The involvement of CCl4 biotransformation mechanism in decreasing the Protein Kinase C activity has been analyzed in hepatocytes isolated from phenobarbital-pretreated rats. A significant inhibition (55%) and an almost total disappearance (87%) of the enzyme activity were observed at 15 min and at 30 min incubation with CCl4, respectively. Cell preincubation with Trolox or desferrioxamine allowed a marked whilst not complete protection of both cytosolic and particulate Protein Kinase C activity. These results show that the CCl4 reactive metabolites play a primary role in hepatocyte Protein Kinase C impairment and suggest that besides lipid peroxidation other mechanisms -possibly a derangement of Ca2+ homeostasis- may be involved in this process.

Animals↗
PubMed1990

Lipid peroxidation and covalent binding in the early functional impairment of liver Golgi apparatus by carbon tetrachloride.

The onset of the lipoprotein secretory block provoked by CCl4 in the whole animal was monitored after purification of liver Golgi membranes. Both lipid transit through the apparatus and hexosylation of the lipoprotein are markedly inhibited 5-15 min after poisoning. Pre-treating the animal with alpha-tocopherol, shown to prevent lipid peroxidation without modifying the covalent binding due to CCl4 metabolites, affords little protection against lipid accumulation in the Golgi, but total preservation of galactosyl transferase activity. While haloalkylation therefore appears to be the major mechanism of damage in the early phases of CCl4-induced derangement of lipid secretion, lipid peroxidation is probably more involved later; this is indicated by the marked, though never complete, protection against fatty liver afforded at 24 h after CCl4 poisoning by supplementation of the membrane with alpha-tocopherol.

Animals↗
PubMed1990

Effects of CCl4 poisoning on metabolism of dolichol in rat liver microsomes and Golgi apparatus.

Carbon tetrachloride (CCl4) poisoning affects glycoprotein processing and maturation at the level of rat liver microsomes and Golgi apparatus. HPLC analysis showed that within 5-60 min after CCl4 administration the levels of total dolichol, free dolichol and dolichyl-phosphate strongly decreased both in total microsomes and in Golgi apparatus. The most marked and early reduction of total dolichol was observed in the secretory membranes of Golgi area already 15 min after CCl4 poisoning. The incubation of CCl4-pretreated isolated hepatocytes with [3H]-mevalonate showed a significant slowing down of the label incorporation into both free-dolichol and dolichyl-phosphate. Moreover, lipid peroxidation might cause alterations in the molecular structure of both free-dolichol and dolichyl-phosphate. A notable prevention of dolichol decrease was observed in animals pretreated with vitamin E. The results suggest that the prooxidant activity of CCl4 is able to affect the metabolism of dolichol either by increasing the oxidative degradation or impairing the biosynthetic pathway.

Animals↗
PubMed1988

Carbon tetrachloride-induced inhibition of protein kinase C in isolated rat hepatocytes.

Isolated rat hepatocytes exposed to CCl4 showed a dramatic decrease in [32P] incorporation into proteins which was evident as early as 5 min after the haloalkane addition. DEAE cellulose separation of protein kinases present in both particulated and cytosolic fractions of hepatocytes revealed that only the calcium and phospholipids dependent protein kinase C was affected by the treatment with CCl4, while kinases not requiring these factors for their activity were unmodified. Several 4-hydroxyunsaturated aldehydes known to be produced during CCl4-stimulated lipid peroxidation were found to inhibit protein kinase C at micromolar concentrations, suggesting the possibility that peroxidative events might be responsible for the impairment of protein kinase C during CCl4 intoxication.

Aldehydes↗
PubMed1988

Phosphatidylserine increases in vivo the synaptosomal uptake of exogenous GABA in rats.

A sonicated liposome suspension of gamma-aminobutyric acid (GABA) and phosphatidylserine (liposome-entrapped GABA), intraperitoneally administered in rats, inhibited EEG epileptic activity induced by penicillin, whereas GABA did not. A significant increase (20.4%) in brain radioactivity accumulation occurred at 5 min after i.p. administration of [14C]GABA associated with phosphatidylserine in comparison with the administration of [14C]GABA; such an increase persisted after 20 min. However, the accumulation of radioactivity into brain synaptosomes demonstrated a 24.1% increase at 5 min and subsequently showed a 43.3% increase at 20 min after injection of liposome-entrapped GABA. The above findings suggest that phosphatidylserine stimulates exogenous GABA uptake into brain GABAergic nerve terminals.

Animals↗
PubMed1987

Inhibition of liver Golgi glycosylation activities by carbonyl products of lipid peroxidation.

The present report deals with the investigation of the effect of 4-hydroxy-trans 2,3-nonenal (HNE), hexanal (HEX) and malondialdehyde (MDA), the major products of lipid peroxidation, on the glycosylation pathway of rat liver Golgi apparatus. Defined concentrations of the aldehydes were added to isolated fractions of formative (F3) and secretory (F1 + F2) Golgi compartments, then incubated at 37 degrees C for 10 min. At the end of the incubation the activity of galactosyl-(GT) and sialyl-(ST)transferases, the main enzymes of the terminal protein and lipoprotein glycosylation, was evaluated. A significant impairment of both these activities was observed with HNE and HEX but not with MDA. These data suggest that aldehydes generated during peroxidation reactions are able to impair the protein and lipoprotein maturation mechanism which is normally achieved through a complete glycosylation.

Aldehydes↗
PubMed1986

Investigation of the role of ubiquinone in rat liver subcellular compartments.

The role of ubiquinone in the Golgi apparatus is still unknown, even if it might be considered as a lipid marker of the Golgi compartment because of its high content in these subcellular fractions. In vivo modulation of ubiquinone with ethanol and in vitro pentane extraction show that ubiquinone is not required either for NADH-ferricyanide reductase, acetaldehyde dehydrogenase activity, or Ca2+ and Mg2+ stimulated ATPases. Since ubiquinone does not seem to be involved in these enzymic activities in Golgi compartments, other possible functions are discussed, related to a role in membrane fluidity or as a barrier to the propagation of free radicals.

Aldehyde Oxidoreductases↗
PubMed1985

Carbon tetrachloride-induced inhibition of hepatocyte lipoprotein secretion: functional impairment of Golgi apparatus in the early phases of such injury.

Functional change of liver Golgi apparatus during carbon tetrachloride (CCl4) poisoning was demonstrated both in rat isolated hepatocytes and in the whole animal. The "in vitro" experimental model provided evidence of Golgi derangement early after giving the haloalkane. The "in vivo" analyses also showed that such an alteration involves both formative and secretory sides of the subcellular structure.

Animals↗
PubMed1984

Phospholipids, vitamin A and ubiquinone of the Golgi apparatus subfractions from rat liver after acute ethanol intoxication.

Previous investigations from our laboratory have shown that during acute ethanol intoxication the Golgi apparatus seems involved in impaired dismission of lipoproteins. In the present paper the phospholipid distributions of Golgi subfractions have been analyzed in livers of normal and ethanol intoxicated rats. No significant differences in the phospholipid classes have been observed in this study. On the contrary, a decrease of vitamin A and ubiquinone in Golgi subfractions is evident. The results are briefly discussed in view of the role played by these endogenous antioxidants in the Golgi membranes and in the pathogenesis of ethanol induced fatty liver.

Alcoholic Intoxication↗
PubMed1984

Phospholipids of Golgi subfractions determined with an enzymatic method.

Golgi apparatus subfractions are still under consideration both for morphological, biochemical and functional characterization. In this note, we determined glycerophospholipids and Golgi subfractions from rat liver by a method that requires the complete enzymatic hydrolysis of phospholipids with phospholipase C from CL perfringens. The main advantages of this procedure are that small amounts of protein membranes are required, the precision and the rapidity.

Animals↗
PubMed1978

Effects of cicloxilic acid on liver subcellular fractions triglyceride content in acute ethanol intoxication.

The action of cis-2-hydroxy-2-phenyl-cyclohexanecarboxilic acid (cicloxilic acid) on the concentration of triglycerides in the subcellular compartments of the liver was investigated in acutely ethanol-intoxicated rats. Cicloxilic acid is able to significantly reduce the accumulation of neutral fats in the homogenate and in the cytosol and to shorten the steatosis regression time. The triglyceride content in total microsomes results slightly higher in the animals treated with cicloxilic acid than in those treated with ethanol only. The data are discussed in relation to the pathogenesis of ethanol fatty liver and to the possible mechanism of action of cicloxilic acid.

Alcoholic Intoxication↗
PubMed1978

Influence of cicloxilic acid on energy production by hepatocyte mitochondria during acute ethanol intoxication.

Liver mitochondria from acute ethanol intoxicated rats show a highly significant uncoupling of oxidative phosphorylation. cis-2-Hydroxy-2-phenyl-cyclohexanecarboxylic acid (cicloxilic acid) early normalizes the P/O ratio and, therefore, the mitochondrial energy producing mechanisms. The significance of these phenomena and the possible role of cicloxilic acid on mitochondrial energy-production are discussed.

Alcoholic Intoxication↗
PubMed1978

Influence of cicloxilic acid on the intracellular transport of 3H-palmitic acid during acute ethanol fatty liver.

cis-2-Hydroxy-2-phenyl-cyclohexanecarboxilic acid (cicloxilic acid) modifies the rat's hepatocyte intracellular movements of 3H-palmitic acid in the course of fatty liver by acute ethanol intoxication. It counteracts the impairment of radioactive lipid uptake due to ethanol treatment and promotes the early and complete release of the radioisotope inhibited by ethanol. The relevance of these results to the role of changes in the intracellular transport systems in the pathogenesis of ethanol steatosis is discussed. This and previous studies show that cicloxilic acid acts by stimulating the intracellular lipoprotein transport probably preventing by this mechanism the ethanol induced liver injury.

Animals↗