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Biomedical subjects

F A Kummerow

Publications and source records attributed to F A Kummerow.

At least 73 records · Page 4Linked to original sources

Changes of linoleic acid metabolism and cellular phospholipid fatty acid composition in LLC-PK cells cultured at low magnesium concentrations.

LLC-PK cells grown on media containing normal (480 microM) or reduced magnesium levels (25, 6.3 or 2.5 microM) were used to study the effect of magnesium deficiency on linoleic acid metabolism and cellular membrane fatty acids. The fatty acid composition of the cellular phospholipids showed a significant decrease in 20:4(n-6) and 22:4(n-6) acids and a significant increase in 18:2(n-6), 18:3(n-6) and 20:3(n-6) fatty acids in magnesium-deficient cells compared to magnesium-sufficient cells. When [1-14C]linoleic acid was incubated with control (480 microM Mg2+) or magnesium deficient cells (2.6 microM Mg2+) the rate of tetraenoic acid synthesis (20:4(n-6) + 22:4(n-6) was significantly reduced in magnesium-deficient cells, indicating that the metabolic conversion of 18:2(n-6) to 20:4(n-6) is impaired in magnesium deficiency. This reduction in conversion may be due to the impairment of either the delta(5)- or the delta(6)-desaturase, or both. This study shows that magnesium deficiency perturbs essential fatty acid (EFA) metabolism and decreases the cellular membrane polyunsaturated fatty acid (PUFA) content. These alterations are likely to have adverse effects on cellular membrane properties and functions.

Animals↗

Changes in phospholipid composition and calcium flux in LLC-PK cells cultured at low magnesium concentrations.

Monolayers of porcine kidney cells (LLC-PK) were grown in a series of Nu-Serum-supplemented media containing different Mg(2+) concentrations (480, 250, 25, 6.3 or 2.6 microM) to study the effect of Mg(2+) depletion on cellular phospholipid changes and the consequent effect on the membrane permeability to Ca(2+). Cells grown on 6.3 or 2.6 microM Mg(2+) showed a decrease in PE, PS, Sph, PI and an increase of PC. These changes were attributed mainly to the decreased rate of Sph synthesis through the transfer of phosphocholine from PC to ceramide, or due to the increase of PE N-methylation as found in Mg(2+)-deficient cells. The (45)Ca uptake was increased in cells grown on 25.0 microM Mg(2+), while it was decreased in cells grown on 6.3 or 2.6 microM Mg(2+). These changes in Ca(2+) uptake were related to changes of cellular phospholipids and fatty acids which affect adenylate cyclase activity in the membrane, as well as the membrane fluidity.

Animals↗

Esterification of dehydroepiandrosterone by human plasma HDL.

Evidence for metabolic esterification of dehydroepiandrosterone (DHEA) in human blood plasma, identification of the active lipoprotein (LP) subclass involved, namely HDL3, as well as positive identification of the long-chain fatty acid esters of DHEA formed as incubation products is presented. The esterification reaction of DHEA and subsequent transfer and transport of DHEA esters in human plasma appears to proceed in a manner similar to that of cholesterol. The experiments presented serve as a model predicting similar metabolic transformations during HDL3 interactions with other steroid hormones that have the delta 5-3 beta-hydroxy steroid ring structure and exhibit nonequilibrium associations with HDL. These observations imply that significant quantities of DHEA, particularly in the conjugated ester form, can enter cells via the membrane receptor-mediated pathways of LP internalization.

Dehydroepiandrosterone↗

Effect of magnesium deficiency on delta 6 desaturase activity and fatty acid composition of rat liver microsomes.

Experimental Mg2+ deficiency was induced in a group of rats by feeding them a Mg2+-deficient diet for 23 days. They were pair-fed to compare with a control group of rats fed a Mg2+-sufficient diet. In the Mg2+-deficient group the plasma total cholesterol and triglyceride levels were increased while HDL-cholesterol was decreased. In the Mg2+-deficient group the plasma level of thiobarbituric acid reacting substances (TBARS) used as a measure for lipid peroxidation was increased. The increase was attributed to the increased cytosolic Ca2+ in Mg2+-deficiency which can cause: 1) increase of hydro and endoperoxide levels as a consequence of the increase of arachidonic acid release and eicosanoid synthesis in Mg2+-deficiency, and 2) inhibition of the mitochondrial respiratory activity and activation of Ca2+-dependent proteases which may activate the conversion of xanthine dehydrogenase to xanthine oxidase which generates active O2 species. In the Mg2+-deficient group, the fatty acid composition of the liver microsomes indicated a slower rate of conversion of linoleic acid to arachidonic acid which was consistent with the decrease of delta 6 desaturase activity in liver microsomes of Mg2+-deficient rats as measured in vitro. The decrease of delta 6 desaturase activity was attributed to the lower concentration of actual enzyme molecules as a result of the decreased rate of protein synthesis in Mg2+-deficiency. The possible effects of the increased catecholamine release in Mg2+-deficiency are discussed.

Adenosine Triphosphate↗

Effect of dietary vitamin E on plasma lipids and atherogenesis in restricted ovulator chickens.

Restricted ovulator hens, which develop hyperlipidemia, were fed 1000 IU vitamin E per k of diet. These hens maintained their hyperlipidemia but plasma peroxide levels were reduced to those of laying hens. The intimal thickness of the aorta was measured by light microscopy. Hyperlipidemic hens which had high plasma peroxide levels had an increased intimal thickness as compared to laying hens. Hyperlipidemic hens which had their plasma peroxide levels reduced by dietary vitamin E had intimal thicknesses the same as laying hens. It is suggested that hyperlipidemia without lipid peroxidation either does not promote atherogenesis or does so at a reduced rate.

Animals↗

Effects of estrogen-induced hyperlipidemia on the erythrocyte membrane in chicks.

The effects of estrogen-induced hyperlipidemia on plasma lipid peroxidation, fatty acid composition and osmotic fragility of erythrocytes in chickens were studied. Young male chickens implanted with estrogen for three wk developed a marked hyperlipidemia. Plasma levels of triglyceride, cholesterol and phospholipid were elevated 68-, four- and 24-fold, respectively, over controls. There was also a two-fold increase in plasma lipid peroxidation measured by the thiobarbituric acid test. Vitamin E supplement (1,000 IU/kg diet) reduced the plasma lipid peroxidation to the control level, but had no effect on the plasma lipid content. Estrogen-induced hyperlipidemia resulted in changes in the fatty acid composition of membrane lipids of erythrocytes. The major changes were an increase in oleic acid from 10.0% to 14.2% and a decrease in linoleic acid from 31.3% to 26.0%. The erythrocytes with an altered membrane fatty acid composition were found to have an increased osmotic fragility. It was apparent that there was a direct correlation between the oleic acid content and the osmotic fragility of erythrocytes.

Animals↗

Serum factors which alter cell membranes.

Mammalian cell membranes are much more sensitive to changes in serum ion concentrations than they are to serum cholesterol. Because of this, arterial cells function normally only in a very narrow range of serum ion concentrations. Unfortunately, new introductions into the food supply have been made in the diet since 1920 which may perturb the delicate relationships between arterial cell membranes and the blood serum to which they are exposed. For example, powerful surface active agents are used to emulsify fats in a host of popular food items. None of them have been adequately tested for their possible role in changing phospholipid head group composition of arterial or myocardial cell membranes. Ocean salt has been replaced by refined table salt removing a rich source of magnesium from the diet of Northern Europeans and Americans. Excessive amounts of Vitamin D, which may calcify soft tissue, have been added to the diet as a means of preventing a disease that does not develop in babies exposed to sunshine. The introduction of hydrogenated vegetable oil to the diet has helped to stimulate per capita fat consumption to almost twice the level of 1920. How the introduction of such technology has changed arterial cell membrane structure or function has not been considered. It is now possible to consider the influence of this technology on the food supply by the application of modern genetic engineering methods. The application of this type of methodology in the study of cholesterol metabolism and its role in atherosclerosis may help to find means of preventing heart disease and strokes.

Animals↗

Lipid oxidation in plasma and tissues from estrogenized chicken hens.

Four groups of 5-month-old chicken hens were given estradiol treatments and/or 5% dietary oil supplement for 14 days, after which blood plasma, liver, heart, and skeletal muscle were analyzed for lipid oxidation by TBA assay for malonaldehyde. Plasma from estradiol-treated birds had 8-fold higher levels of malonaldehyde compared to untreated birds. The bulk of this effect was due to a 5-fold increase in plasma lipid, but this lipid also contained a 70% higher concentration of malonaldehyde. Estradiol treatments produced significantly increased TBA numbers in liver, heart, and skeletal muscle. Corn oil supplementation significantly increased the malonaldehyde concentration in fat extracted from liver and heart, but not from plasma or skeletal muscle. It was concluded that estradiol treatment, in addition to generally increasing the deposition of fat in plasma and organs, also enhanced the concentration of malonaldehyde equivalents in plasma and organ fat.

Animals↗

Dietary magnesium effect on swine coronary atherosclerosis induced by hypervitaminosis D.

The effects of magnesium (Mg) supplement on coronary arteries of 61 swine, fed various levels of vitamin D3 (VD3), were studied by light and electron microscopy. High frequencies of smooth muscle cell degeneration were observed in groups of swine fed various levels of excess VD3. Swine fed moderately excessive level of VD3 with a basal level of Mg displayed great incidence and magnitude of intimal thickening, while swine fed the same level of VD3 with supplementary Mg sustained only mild intimal thickening. In groups of swine fed high levels of VD3, the prevention of calcification and smooth muscle cell degeneration was observed as a supplementary Mg effect. Plasma analyses indicated that supplementary Mg with excess VD3 increased cholesterol levels but decreased arterial damage. It is concluded that the dietary Mg supplement prevents coronary atherosclerosis induced by hypervitaminosis D.

Animals↗

Effects of postnatal protein undernutrition on myelination in rat brain.

Pups were subjected, from birth, to protein undernutrition by feeding the lactating dams 8% casein (CS) or 8% soy protein (SP) diet up to weaning; the weanlings were fed the same diets until 6 weeks of age. At 3 and 6 weeks of age, myelin was isolated from the brains and characterized. The quantities of myelin and its content of cholesterol, galactolipids and phospholipids, were significantly depressed in the 8% CS and 8% SP groups but not when soy protein was fed at the same level as casein (25%) in the control. Furthermore, the severity of the deficits in myelination showed a differential pattern depending on the type of dietary protein fed. At weaning, the deficits with the 8% SP diet were 1.5-2.0-times greater than with the corresponding casein diet. A more pronounced retardation in the initiation, progression and capacity of myelination in postnatal soy protein undernutrition was indicated.

Animals↗

Effect of magnesium deficiency on ultrastructural changes in coronary arteries of swine.

The effects of magnesium (Mg) deficiency on the coronary arteries of 27 Yorkshire swine were studied by light and electron microscopy. The experimental animals were divided into 4 groups which received the following supplements: Group I, basal ration with adequate Mg (540 mg/kg diet), Group II, basal ration with insufficient Mg (270 mg/kg diet) Group III, 10% milk powder with adequate Mg (540 mg/kg diet), Group IV, 10% milk powder with insufficient Mg (270 mg/kg diet). Serum analysis indicated that dietary low Mg supplementation decreased cholesterol levels and increased phospholipid concentrations significantly. The highest magnitude and incidence of intimal thickening were observed in the coronary arteries of Group IV (p less than 0.003). No significant intimal thickening was detected in any of the other groups. Ultrastructural studies revealed a greater frequency of degenerated cells in Group III and IV (p less than 0.01). Numerous calcifications were observed in only Group IV. These data suggest that moderate Mg deficiency can promote atherosclerosis in combination with some atherogenic diet, and that the presence of smooth muscle cell degeneration is important in order for a magnesium deficiency to exert an effect on the coronary artery of swine.

Animals↗

Induction of serum lipid peroxidation in chickens.

Lipid peroxidation has a known association with, but an unknown role in atherosclerosis. In order to separate the possible effects of serum lipid peroxidation from hyperlipidemia it is necessary to be able to independently manipulate these two variables. We here explore methods to raise serum peroxidation while not affecting serum lipid levels in the chickens. Pullets were injected with corn oil, injected with corn oil while feeding 1% cholesterol and injected with malondialdehyde in corn oil. Each of these treatments elevated serum peroxidation while leaving triglyceride levels unchanged. The effect of each treatment was the same and it is concluded that injection of malondialdehyde or injections of corn oil while feeding cholesterol have no advantage over injections of corn oil alone.

Animals↗

Comparison of liposome entrapment parameters by optical and atomic absorption spectrophotometry.

Methods for the complete characterization of liposomes prepared by ether-injection are described in detail. The validity of atomic absorption spectrophotometry for measuring markers of trapped volume was checked by comparative determinations of markers with established optical spectrophotometrical methods. The favorable results using atomic absorption spectrophotometry to quantitate the marker Mn2+ are of particular relevance as manganese ion is also the paramagnetic probe in n.m.r. measurements of water permeability of liposomes; our results indicate that in such measurements no other marker need be incorporated.

Liposomes↗

Plasma lipid peroxidation in hyperlipidemic chickens.

Laying and genetically defective non-laying hens were evaluated for plasma lipid and plasma peroxidation levels. The non-layers developed extreme hyperlipidemia as well as greatly increased levels of lipid peroxidation. It was concluded that the concurrent presence of lipid peroxidation products must be considered when evaluating hyperlipidemic causes of atherosclerosis in the chicken.

Animals↗

Coronary arterial lesions in piglets from sows fed moderate excesses of vitamin D.

Ultrastructural studies were conducted on the coronary arteries of 6 week-old piglets from sows which received diets containing either 25 micrograms or 3.7 micrograms of vitamin D3 per pound of basal ration. The subendothelial space which was rich in mucopolysaccharide and newly formed tiny elastic fibers, contained numerous macrophages, some of which possessed lipid droplets. Degenerated smooth muscle cells with pyknotic nuclei or vesiculated organelles, and mitotic smooth muscle cells were occasionally seen in the coronary artery. Piglets from sows which were fed high doses of vitamin D had more degenerated smooth muscle cells without stainable lipid and lipid containing cells in their coronary arteries than piglets from sows which were fed low doses of vitamin D. These results suggested that an excess dietary intake of vitamin D by pregnant animals may have potential angiotoxic effects on the coronary arteries of their offsprings.

Animals↗