PubMed Health⌕ Search

Biomedical subjects

J Polonovski

Publications and source records attributed to J Polonovski.

At least 19 recordsLinked to original sources
PubMed1990

[The modification of high density lipoproteins by malondialdehyde changes their interaction with J774 macrophages and decreases cholesterol cell efflux].

The treatment of HDL3 with malondialdehyde (MDA) results in an increase of the electrophoretic mobility of the particle and in aggregation of the apolipoprotein AI. The binding of MDA-treated-HDL3 to murine macrophages J774 is decreased, as compared to native HDL3. The cholesterol efflux is also markedly reduced. In view of the fact that MDA is produced following plaquette aggregation or oxidative stress, the eventual existence of MDA-modified-HOL in vivo might accelerate the appearance of atherosclerotic lesions by reducing cellular cholesterol efflux.

Animals↗
PubMed1989

Arachidonate cannot be released directly from diacyl-sn-glycero-3-phosphocholine in thrombin-stimulated platelets.

The origin of the arachidonate released from platelets on stimulation with thrombin was investigated by comparing the specific activities of released arachidonate and of arachidonoyl-containing phospholipids using rat platelets prelabelled with arachidonate. Quantification of the released arachidonate was determined in the presence of BW 755 C, a dual cyclo-oxygenase/lipoxygenase inhibitor, which was found not to modify the arachidonate mobilization between the platelet phospholipids. The phospholipid molecular species were analysed by h.p.l.c. of diradylglycerol benzoate derivatives of diacyl, alkylacyl and alkenylacyl classes. The labelled/unlabelled arachidonate ratio varied greatly in the phospholipids depending on whether an ether or acyl bond was present in sn-1 position of the glycerol, on the length and degree of unsaturation of this fatty chain and on the polar head group. Between 15 s and 5 min of stimulation by thrombin, the released arachidonate kept a constant specific activity which was considerably lower than the specific activity of diacyl-GPC. The specific activity of the released arachidonate was intermediate between the specific activities of the 16:0-20:4 and 18:0-20:4 species of diacyl-GPI and diacyl-GPE, and corresponded to the mean specific activity of alkylacyl-GPC. The data indicate that the released arachidonate cannot come directly from diacyl-GPC, and that two phospholipids in particular can act as direct precursors of the released arachidonate. These are (1) the alkylacyl-GPC and (2) the diacyl-GPE whose hydrolysis would induce an arachidonate transfer from diacyl-GPC.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗
PubMed1989

Human placental microvilli as a source of antigen for the preparation of a polyclonal antibody directed against the LDL receptor.

Polyclonal antibodies were prepared by immunization of rabbits with partially purified LDL receptor obtained from human placental microvilli. The antiserum reacted with membranes from human placental microvilli and human fibroblasts, as assessed by immunobinding studies. It also reacted with purified LDL receptors of both origins. The antiserum markedly inhibited 125I-labeled LDL binding to cultured human fibroblasts.

Antibody Formation↗
PubMed1988

Cyclic AMP decreases LDL catabolism and cholesterol synthesis in the human hepatoma cell line HepG2.

A 24h pretreatment of the human hepatoma cell line HepG2 with dibutyryl cyclic AMP in the presence of theophylline induced a dose dependent decrease in low density lipoprotein binding, uptake and degradation. This effect is most likely due to a reduction of the LDL receptor number. Sterol synthesis from sodium acetate is markedly inhibited, either in the presence or absence of LDL, whereas synthesis from mevalonic acid is unchanged. Cyclic AMP also induced a decrease in hydroxy methyl glutaryl coenzyme A reductase activity. These effects of cyclic AMP might be involved in some hormonal regulation of the LDL pathway and cholesterol metabolism in the liver.

Acetates↗
PubMed1988

PAF-acether decreases low density lipoprotein degradation and alters lipid metabolism in cultured human fibroblasts.

A 24 h pretreatment of human cultured fibroblasts with PAF-acether (PAF) induced a decrease in LDL degradation and a correlative accumulation of undegraded LDL. LDL binding was not significantly affected. Sterol and triacylglycerol synthesis from sodium acetate was enhanced whereas phospholipid synthesis decreased. Oleic acid incorporation into cholesteryl ester was markedly inhibited, whereas incorporation into triacylglycerols was increased. A decrease in the percentage of phosphatidylcholine and an increase in the percentage of phosphatidylethanolamine were found using sodium [32P]orthophosphate as precursor. These effects of PAF on LDL and lipid metabolism could be related to perturbations in membrane structure characteristics, leading to a delay in LDL delivery to lysosomes, and to modification of the activity of some key enzymes of lipid metabolism.

Cells, Cultured↗
PubMed1988

Electroimmunoassay of human serum lipoproteins containing Apo A-I by monoclonal antibodies.

Three monoclonal antibodies to human serum apolipoprotein (Apo) A-I (4A12, 4B11 and 2G11) were produced by Sanofi. They were directed to three distinct epitopes of the Apo A-I molecule, present on the surface of the lipoprotein particles. They were able to precipitate individually some lipoprotein units from the serum. Only the mixture of the three monoclonal antibodies could allow a precipitation of all Apo A-I containing particles. An electroimmunoassay using this oligoclonal mixture was assessed to standardize the Apo A-I measurement in serum. Results agreed well with those obtained by electroimmunoassays using polyclonal antisera. Moreover no pretreatment of serum samples with dissociating agents or detergents was required. Therefore, this specific, rapid (7-8 h), precise (within- and between-assay precisions were 4.25 and 3.1%, respectively) immunoassay is routinely available for apolipoprotein A-I measurement in serum.

Antibodies, Monoclonal↗
PubMed1988

A new human pathology with visceral accumulation of long-chain n-alkanes; tissue distribution of the stored compounds and pathophysiological hypotheses.

This report deals with a new human disorder characterized by the accumulation of plant long-chain n-alkanes in viscera of a human patient. Lipid analysis of tissues from an adult male after sudden death (affected with diffuse visceral granuloma containing lipophilic crystallized material) showed the presence of abnormal compounds identified as long-chain n-alkanes with 29 (n-nonacosane), 31 (n-hentriacontane) and 33 carbons (n-tritriacontane). Study of n-alkane distribution in patient tissues showed a major accumulation in lumbo-aortic lymph nodes, adrenal glands, lung (the highest levels were found in lung granulomas) and liver; significantly lower amounts were detected in myocardium and kidney, whereas no detectable level was found in brain. On the basis of the structural composition and of the tissue distribution of the accumulated n-alkanes, their dietary (plant) origin and the pathophysiological mechanism of the storage are discussed.

Adrenal Glands↗
PubMed1988

The effects of perhexiline maleate on low density lipoprotein processing and cholesterol metabolism in cultured human fibroblasts.

The effects of perhexiline maleate (PM, Pexid) on low density lipoprotein (LDL) processing and cholesterol metabolism were investigated after a 24 h pretreatment with the drug. Perhexiline maleate increased LDL uptake in the range 10(-6) to 10(-5) M (180% of control for 10(-5) M), whereas LDL binding and degradation were not affected. Sterol synthesis from sodium acetate was enhanced by perhexiline maleate (X 2.2 for 10(-5) M), while cholesterol esterification with oleic acid was decreased (40% of control for 10(-5) M). These effects of perhexiline on cholesterol metabolism are specific, since the synthesis of triacylglycerols from sodium acetate is not affected and since the incorporation of oleic acid into triacylglycerols is much less impaired. The decreased cholesterol esterification is accompanied by a reduction of acylcoenzyme A-cholesterol-O-acyltransferase (ACAT) activity measured in vitro on cell extracts.

Cells, Cultured↗
PubMed1988

Trifluoperazine increases fatty acid turnover in phospholipids in cultured human fibroblasts.

A 24-hr pretreatment of cultured human fibroblasts with trifluoperazine induced a marked increase in incorporation of saturated (stearic, palmitic) and unsaturated (oleic, arachidonic) fatty acids into phospholipids (1.5- to 2-fold for 5.10(-5) M trifluoperazine). Concomitantly, incorporation into cholesteryl esters was strongly inhibited (20% of control for 5.10(-5) M trifluoperazine). The drug did not change the phospholipid composition of treated cells. The effect of trifluoperazine on oleic acid incorporation into phospholipids was time-dependent and reached a maximum after a six-hr preincubation with the drug. Trifluoperazine also induced an increase in the rate of chase of oleic acid from the different phospholipid classes. In vitro preincubation of cell-free extracts with trifluoperazine resulted in activation of phospholipid acyltransferases, whereas cholesterol acyltransferase activity was decreased. The rapid effect of trifluoperazine together with its effect on a cell-free system suggests a direct action of this amphiphilic drug on the acyltransferase activities, probably by modification of the structural organization of cellular membranes.

Cells, Cultured↗
PubMed1988

The antidiabetic drug metformin decreases cholesterol metabolism in cultured human fibroblasts.

The effect of the hypoglycemic biguanide drug Metformin was investigated after a 72 h pretreatment of human cultured fibroblasts. Metformin induced a moderate increase in low density lipoprotein binding, uptake and internalization (25% increase after treatment with 5 X 10(-4) M of drug). A decrease in sterol, fatty acid and triacyglycerol synthesis from sodium acetate was observed after pretreatment with the drug, with a dose-dependent effect in the range of 5 X 10(-5) to 5 X 10(-4) M (50% reduction of sterol synthesis after treatment with Metformin 5 X 10(-4) M). This effect was also observed in fibroblasts from a patient with homozygous familial hypercholesterolemia. Cholesterol esterification studied by incorporation of radiolabeled oleic acid was reduced by Metformin (40% of control after treatment with Metformin 5 X 10(-4) M) whereas incorporation into triacylglycerols was less impaired. These effects of Metformin on cholesterol metabolism were observed either in the presence or in the absence of low density lipoproteins. Moreover, Metformin also reduced cholesterol esterification in J774 monocyte-macrophage cells. Metformin also induced a decrease of hydroxymethylglutaryl coenzyme A reductase activity in cultured fibroblasts and a reduction of acyl-coenzyme A: cholesterol-O-acyltransferase activity in cultured fibroblasts and J774 cells.

Cells, Cultured↗