Alteration of lymphocyte membrane phospholipids and intracellular free calcium concentrations in hyperlipidemic subjects.

Hypercholesterolemia has been proposed to influence cell functions via changes in membrane composition. The aim of the present study was to determine whether the membrane phospholipid composition of human lymphocytes is modified in hypercholesterolemia and whether these changes are accompanied by functional modifications. The phospholipid fatty acid contents and intracellular free calcium concentrations were determined in peripheral blood lymphocytes from 13 subjects with serum total cholesterol levels ranging from 4.

Effect of glibenclamide on the metabolism of fatty acids in cultures of newborn rat heart cells under normoxic and hypoxic conditions.

Several deleterious biochemical alterations have been observed in myocardial cells during ischemia, including perturbations of transmembrane ion equilibria, production of noxious oxygen-derived radicals and loss of membrane phospholipids. Although the precise relationship between these alterations and the reduction of oxygen and glucose supplies is not fully understood, the decrease of intracellular ATP content appears to be a key event in the cascade. Recent evidence suggests that opening of ATP-sensitive K+ channels may constitute an endogenous protective mechanism during ischemia.

Altered phospholipid fatty acid content and metabolism in heart cell cultures from newborn spontaneously hypertensive rats.

Genetic hypertension has been proposed to be associated with impaired lipid metabolism. To investigate whether lipid metabolism is altered in young rats of the spontaneously hypertensive Okamoto strain (SHR), we have compared the phospholipid fatty acid content and metabolism in cultured heart myocytes and fibroblasts from SHR and normotensive Wistar-Kyoto (WKY) newborn rats. The phospholipid-bound fatty acid profile and metabolism were altered in SHR cardiomyocytes and unchanged in SHR fibroblasts.

Regulation of membrane phospholipid metabolism in heart cell culture.

We have isolated, from newborn rats, heart cultures enriched in contractile muscle cells (M) and cultures of fibroblast-like cells (F). M cultures respond to simulated ischemia by an arrest of beating activity, by a decrease in beta oxydation rate, ATP and phosphocreatine content and by a loss of membrane phospholipids associated with neutral lipids accumulation. F cells in contrast do not respond to oxygen deprivation.

Cytosolic pH in cultured cardiac myocytes and fibroblasts from newborn spontaneously hypertensive rats.

Newborn spontaneously hypertensive rats (SHR) develop cardiac hypertrophy before a rise in blood pressure. Cytosolic pH (pHi) has been discovered to modulate cell growth and proliferation; therefore, we have investigated pHi in myocytes and fibroblasts from 3- to 4-day-old SHR and normotensive Wistar (W) and Wistar-Kyoto controls (WKY). The ratio of heart to body weight was higher in SHR than in W and WKY (7.

Effect of isoproterenol on lipid metabolism and prostaglandin production in cultures of newborn rat heart cells, under normoxic and hypoxic conditions.

Catecholamines are known to exert deleterious effects on heart cells and to provoke biochemical alterations similar to those observed during myocardial infarction. In order to investigate the mechanisms of these effects, we have studied in cultures of muscle (M) and fibroblast-like (F) cells derived from newborn rat hearts, the action of isoproterenol on membrane lipid metabolism and on prostaglandin production. We showed in F cells that beta-agonist stimulation produced a striking loss of membrane phospholipids and a moderate hydrolysis of cell triglycerides.

Abnormal fatty acid utilization by cultured cardiac cells from 7-day-old obese Zucker rats.

Fatty acid utilization by muscle and nonmuscle heart cells in culture has been investigated in the 7-day-old Zucker rat to determine if this tissue could contribute to the lower energy expenditure reported in obese rats at the onset of obesity. The partitioning of oleate to oxidation and esterification products and the effect of genotype on this partitioning according to cell types were studied. Results showed that the fatty acid beta-oxidation and its esterification in neutral lipid was decreased by 30% in beating muscle cells from obese animals when compared with those from lean animals.

Effect of oxygen deprivation on metabolism of arachidonic acid by cultures of rat heart cells.

To investigate the mechanisms responsible for the impairment of phospholipid metabolism observed in ischemic cells, we have studied the effect of conditions simulating ischemia on the metabolism of arachidonic acid (AA) by muscle (M-) and nonmuscle (F-) cells isolated from newborn rat hearts and cultured separately. In muscle cells, oxygen deprivation induces a significant stimulation of the release of [14C]AA from prelabeled cells associated with a preferential redistribution of [14C]AA into cell triglycerides but not formation of radioactive prostaglandins. Moreover, the fatty acid content of phospholipids, as measured by capillary gas chromatography, appears markedly reduced in ischemic myocardial cells.

Effect of glucocorticoids on arachidonic acid metabolism and prostaglandin secretion by cultures of newborn rat heart cells.

We described that oxygen deprivation induced in cultures of heart muscle cells, biochemical events similar to those described in ischemic tissue: arachidonic acid liberation, loss of membrane phospholipids and increase in neutral lipids. Since glucocorticoids have been described to inhibit phospholipase activity and to exert beneficial effects during myocardial infarction, we studied in our experimental model the action of dexamethasone on the metabolism of arachidonic acid and on the synthesis of immunoreactive prostaglandins. Our results show that heart muscle cells produce prostaglandin E2 and 6-keto-prostaglandin-F1 alpha.

Growth rate and phospholipase C activity in cardiac and aortic spontaneously hypertensive rat cells.

The cellular proliferation rate and phospholipase C sensitivity have been compared in various cardiovascular cells cultured from spontaneously hypertensive (SHR) and Wistar-Kyoto rats (WKY). Aortic smooth muscle cells from SHR showed an enhanced proliferation rate under the culture conditions (in the presence of 10% fetal calf serum) and hypersensitivity to the mitogenic action of angiotensin II and serotonin. Phospholipase C activity (determined by measuring the formation of tritiated inositol phosphates from [3H]-myoinositol) triggered by angiotensin II was also higher in these cells than in those from WKY.

Effects of various antianginal drugs on sodium influx in rat brain synaptosomes and in rat heart muscle cells in culture.

This paper describes the inhibitory effects of several antianginal drugs on 22Na uptake of the fast Na+ channel in rat brain synaptosomes and in rat heart muscle cells in culture. Calcium antagonists like verapamil, flunarizine, perhexiline, two perhexiline derivatives IPS 629 and IPS 672, and beta-adrenoceptor antagonists like propranolol and practolol were tested. IPS 672 was the most active compound on synaptosomes and heart muscle cells (IC50 = 2.

The effect of 4'-deoxypyridoxine on rat heart cell cultures under oxygen deficiency.

The purpose of this work was to study the consequences of an intracellular depletion of pyridoxal-phosphate (PLP) in rat heart cells in culture submitted to oxygen deficiency. Glucose (GLc) and 4'-deoxypyridoxine (DOP) effects were separately evaluated after 150 mn of partial oxygen deprivation (N2) with regard to enzyme leakage, beating rates, intracellular concentrations of PLP and the ratio glycogen phosphorylase activity (-5'-AMP/+5'-AMP). PLP concentrations were higher in the air-GLc group than in the air group.

[Indices of partial oxygen deprivation in the culture medium of cardiac cells].

Three indexes of partial oxygen deprivation, i.e. hypoxanthine, alpha HBDH and CK, were investigated in rat heart cell cultures, 7 day-old.

Comparison of the chronotropic effect and the cyclic AMP accumulation induced by beta 2-agonists in rat heart cell culture.

1 The chronotropic response and the variation in cyclic adenosine 3',5'-monophosphate (cyclic AMP) accumulation induced by isoprenaline and six beta 2-selective agonists (fenoterol, salmefamol, soterenol, zinterol, salbutamol and formoterol) were analyzed on cultured heart cells of the rat. 2 The compounds elicited an enhancement of the frequency, but the time course of the variation of the beating rate was not identical for all of them. A rapid onset was observed for isoprenaline, zinterol and formoterol while it was slower for fenoterol, salmefamol and salbutamol.

[Optimal trypsin concentration for rat heart cell cultures].

Three concentrations (0.5, 1 and 2 per 1000, w/v) of a single batch of trypsin were compared regarding their influence on cultured cardiac cell of newborn rats. All three allowed to obtain cardiac cells in good conditions, as evidence by beating frequencies and [16-14C]-palmitate beta-oxidation.

[Influence of the oxygenation state of the culture media on the level of non esterified fatty acids and of cholesterol in heart cells of the newborn rat].

The uptake of non esterified fatty acids (NEFA), from a medium supplemented with 10% of calf serum, by rat myocardial cells cultured during 8 days, without renewal of the medium, was identical whatever the values of partial pressures of oxygen in the medium. Cellular cholesterol level was reduced when air or oxygen (+5% CO2) was blown into culture bottles; it was enhanced by gassing with nitrogen 24 h later. Cellular NEFA level was reduced by air, but not by oxygen blowing; it was enhanced by gassing with nitrogen 24 h later.