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Biomedical subjects

J Polonovski

Publications and source records attributed to J Polonovski.

At least 55 records · Page 3Linked to original sources
PubMed1986

Phorbol esters inhibit low density lipoprotein processing by cultured human fibroblasts.

A 24 h pretreatment of MRC5 fibroblasts with the protein kinase C activator 12-O-tetradecanoylphorbol 13-acetate (TPA) induced a marked decrease in low density lipoprotein (LDL) internalization and degradation; the maximal effect (about 55% decrease) was observed for 10(-7) M TPA. LDL binding was reduced about 35-40%. A significant decrease (about 25%) in LDL internalization was observed after a 2 h incubation of cells with the drug, but longer incubation times (4-6 h) led to a greater effect. Another tumor promoter, phorbol 12,13-dibutyrate decreased LDL internalization by about 35%, whereas the non-tumor promoting 4 alpha-phorbol 12,13-didecanoate had no effect. The protein kinase C inhibitor alpha-cobrotoxin partially antagonized the inhibitory effect of TPA on LDL internalization. The non-phorbol tumor promoter mezerein, another protein kinase C activator, decreased LDL uptake by about 50%. Finally, it was found that TPA had no significant effect on the affinity of the receptor for the LDL. These results suggest a role for protein kinase C in the LDL pathway in cultured human fibroblasts.

Cell Line↗
PubMed1986

Cyclic AMP increases incorporation of exogenous fatty acids into triacylglycerols in hamster fibroblasts.

Incorporation of various exogenous saturated or unsaturated [14C]labeled fatty acids (palmitic, stearic, oleic, linoleic and arachidonic) into triacylglycerols by hamster fibroblasts was markedly enhanced (two- to fourfold) in the presence of theophylline or dibutyryl cyclic adenosine monophosphate (dbcAMP). This effect was observed for short-term (1-6 hr) as well as long-term (15-24 hr) preincubation with dbcAMP. In the presence of sodium fluoride, a phosphoprotein phosphatase inhibitor, measurement of diacylglycerol acyltransferase (DGAT) activity in cells pretreated with dbcAMP pointed out a marked increase (3 X) in specific activity. The results suggest that DGAT activity in fibroblasts could be activated by a cAMP-dependent phosphorylation process.

Acyltransferases↗
PubMed1986

Early increase in phosphatidyl choline synthesis by choline and transmethylation pathways in spreading fibroblasts.

Phosphatidyl choline (PC) synthesis in trypsinized and reattaching fibroblasts during the spreading state was studied by incorporation of [14C]choline and [methyl-14C]methionine. The choline and phosphatidyl-ethanolamine (PE) transmethylation pathways were both transiently increased about 2-fold during the first 2 h after replating. Maximum increase appeared to be simultaneous with maximum spreading. Incorporation of [32P]orthophosphate showed that the increase in PC synthesis was specific and most probably related to establishment of cell-substrate adhesion sites.

Animals↗
PubMed1986

Detection of distinct receptors for native and acetylated low-density lipoproteins in human placental microvilli by ligand-immunoblotting.

Ligand-immunoblotting was used to detect distinct receptors for native low-density lipoprotein and for acetylated low-density lipoprotein on microvillous membranes from human term placentas. Antisera directed against native and modified low-density lipoproteins were prepared in rabbits and their specificities were assessed by immunodiffusion and immunoelectrophoresis. The receptor for low-density lipoprotein was detected as a 160 kDa protein and that for acetylated low-density lipoprotein as a 200 kDa protein. These receptors were compared with their counterparts in cultured human skin fibroblasts, bovine adrenal cortex and J774 macrophage-like cells. This is the first investigation that visualizes the presence of receptors for both native and modified low-density lipoproteins in a steroidogenic tissue.

Acetylation↗
PubMed1986

[Changes in the biosynthesis, esterification and efflux of cholesterol in fibroblasts in culture from patients with Niemann-Pick disease type C].

Cholesterol synthesis, esterification and efflux have been comparatively studied in control fibroblasts and in fibroblasts from patients with Niemann-Pick disease type C (NPC). Sterol synthesis was markedly increased in NPC cells as compared to controls, either in whole medium or in medium devoid of lipoproteins. 14C-oleic acid incorporation into cholesteryl-esters was 2 to 3 fold reduced in NPC cells, and esterification of 14C-exogenous cholesterol was dramatically (15-30 fold) decreased. ACAT activity, measured in vitro, was not significantly altered in NPC cells. Finally, cholesterol efflux appeared to be decreased in NPC fibroblasts as compared to controls. The hypothesis of a defect in exogenous cholesterol access to intracellular regulatory pools is proposed.

Cells, Cultured↗
PubMed1986

[Structure and metabolism of lipoproteins].

Lipoproteins constitute in plasma a dynamic system allowing lipid transport. For this purpose, apolipoproteins play a very important part. They control and regulate lipid transfer between lipoproteins themselves and among cells, from their hepatic as intestinal synthesis sites to their hepatic as peripheral degradation sites. Enzymatic systems and specific receptors are involved to operate this metabolic pathway.

Chemical Phenomena↗
PubMed1986

[Catabolism of low-density lipoproteins via receptors and its regulation].

Low density lipoproteins (LDL) are the main plasmatic carrier of cholesterol through the tissues. Their catabolism depends essentially on the presence of high affinity specific receptors on the surface of the cells. Every diminution, genetic (familial hypercholesterolemia) or acquired, of the LDL catabolism via the receptors, causes the acceleration of the formation of atheromatous lesions. The present review considers the main characteristics of the receptor, the mechanisms of the endocytosis of LDL, the different types of mutation affecting the catabolism of LDL in familial hypercholesterolemia, as well as certain data concerning the regulation of the catabolism of LDL via the receptors (hormonal effect, effect of AMP, of calcium and role of nutritional factors).

Cholesterol↗
PubMed1985

Epinephrine decreases low density lipoprotein processing and lipid synthesis in cultured human fibroblasts.

The effect of epinephrine on 125I-low density lipoprotein (LDL) uptake and cholesterol metabolism was investigated after a 24 hours pretreatment of cultured human fibroblasts. Epinephrine decreased LDL uptake (binding + internalization) and degradation in a dose-dependent manner. Cholesterol synthesis from 14C sodium acetate and cholesterol esterification measured by 14C oleic acid incorporation into cholesteryl esters were also decreased. These results are in agreement with the general view that epinephrine increases cyclic AMP intracellular level, as it was previously demonstrated that dibutyryl cyclic AMP or isoproterenol treatment of cultured fibroblasts had similar effect on these pathways. The decrease in LDL processing induced by epinephrine could be involved in the worsening effect of epinephrine on atherosclerosis.

Cells, Cultured↗
PubMed1984

Effects of the calcium ionophore A 23187 on low-density lipoprotein processing and lipid metabolism in cultured human fibroblasts.

Pretreatment of cultured human fibroblasts with the calcium ionophore A 23187 resulted in a decrease in low-density lipoprotein internalization. This effect was dose-dependent and did not occur in a medium devoid of calcium. About 2-fold reduction was observed with 10(-5)M A 23187. In contrast, the low-density lipoprotein binding was only slightly affected. The incorporation of [14C]acetate and [14C]oleate into all classes of lipids (sterol, triacylglycerols and phospholipids) was strikingly reduced by ionophore pretreatment.

Acetates↗
PubMed1984

Effects of AY 9944 on low density lipoprotein metabolism in cultured human fibroblasts.

Treatment of cultured human fibroblasts with the hypocholesterolemic drug AY 9944 resulted in a marked increase in low density lipoprotein internalization and degradation for concentrations up to 5 X 10(-6)M. Low density lipoprotein binding was less affected. Concentrations above 5 X 10(-6)M resulted in a relative decrease in low density lipoprotein degradation, whereas binding and internalization plateaued. The stimulation of low density lipoprotein internalization took place within the first hours of incubation of cells with the drug, which suggests a direct effect on the cell membrane. Such phenomenon could account at least partially for the hypocholesterolemic effect of the drug, besides its inhibitory effect on 7-dehydrocholesterol reductase.

Cell Line↗
PubMed1984

Inhibitory factor of phospholipase A2 in normal human serum.

Normal human serum and plasma were shown to contain a factor inhibiting phospholipase A2. This factor has been separated from human serum and plasma by chromatography on a Blue-Ultrogel column and was eluted by tris-HCl buffer (pH 7.2); the proteins eluted by 1 M NaCl-tris HCl buffer exhibited phospholipase A2 activity. This activity was abolished when the inhibitory factor was added to proteins possessing such activity. The inhibitory factor was not dialysable, sensitive to both heat and trypsin treatment, suggesting that it is a protein. In vitro, the same factor inhibited phospholipase A2 rat serum.

Animals↗
PubMed1984

Binding of a spin-labelled chlorpromazine analogue to calmodulin.

The binding of a spin-labelled derivative of chlorpromazine to calmodulin was investigated by e.s.r. spectrometry. The completion of the spectroscopic changes requires the presence of 4 Ca2+ ions per calmodulin molecule. The influences of various physicochemical factors (pH, ionic strength) are discussed in relation to the nature (hydrophobic and polar) of the interactions that hold the drug-calmodulin complex together.

Calcium↗
PubMed1984

Impairment of exogenous sphingomyelin degradation in cultured fibroblasts from familial hypercholesterolemia.

The degradation of exogenous sphingomyelin was investigated in cultured fibroblasts from normal subjects and subjects with familial hypercholesterolemia, either in whole medium or in lipoprotein-deficient medium. When introduced in whole medium, sphingomyelin degradation was significantly decreased (about 1.5-fold) in heterozygotes, and dramatically (about 4-fold) in homozygotes from familial hypercholesterolemia. Sphingomyelinase activity, measured in vitro by conventional methods, was not altered in fibroblasts from familial hypercholesterolemia. The sphingomyelin uptake was notably lower in familial hypercholesterolemia than in controls. The decrease in exogenous sphingomyelin degradation was also found in lipoprotein-deficient medium, suggesting that it is not related to the low density lipoprotein receptor impairment which exists in familial hypercholesterolemia. These results are discussed in relation to sphingomyelin and cholesterol metabolism, and possible abnormalities of the cell membrane in familial hypercholesterolemia are suggested.

Cells, Cultured↗
PubMed1984

1-Acyl-lysolecithin acyltransferase and synthesis of biliary lecithins in rat liver.

The role of lysolecithin acyltransferase activities in biliary lecithin formation was investigated, using livers perfused in the presence of labeled palmitoyl-lysolecithin and albumin, overloaded or not with linoleic acid. At the end of liver perfusion, the lecithins extracted from microsomes, mitochondria and plasma membranes displayed the same specific activity. Double-labeled lysolecithin was used to prove that labeled lecithins were synthesized by lysolecithin acylation. In the absence or presence of a linoleic acid overload, the level of lysolecithin incorporation into linoleyl and arachidonyl containing lecithin was identical. Hence fatty acids did not influence phosphatidylcholine synthesis by the acylation pathway. In vitro the rate of linoleyl lecithin synthesis was the same in plasma membranes, mitochondria and microsomes provided the linoleyl-CoA concentration was lower than 30 microM. Taurocholate was essential to the excretion of lecithin synthesized from lysolecithin and stimulated its synthesis. The specific activities of the two lecithin molecular species excreted in bile (linoleyl and arachidonyl) were not significantly different. These results enabled us to evaluate the contribution of the lysolecithin pathway to the synthesis of lecithin in liver and bile: this contribution in bile was less than 2% under the perfusion conditions used.

1-Acylglycerophosphocholine O-Acyltransferase↗