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Nandrolone decanoate reduces serum lipoprotein(a) concentrations in hemodialysis patients.

We have studied the changes in the lipid profile of 14 chronic hemodialysis patients receiving a 6-month cycle of nandrolone decanoate as treatment for anemia. Nandrolone decanoate was administered in a weekly intramuscular dose of 200 mg and resulted in an increase in the hemoglobin concentration (baseline, 7.9 +/- 0.9 g/dL; month 6, 10.8 +/- 1.7 g/dL; P < 0.001, ANOVA) and also produced relevant modifications in the lipid concentrations. The most significant finding was a decrease in the concentration of lipoprotein(a) [Lp(a)]: baseline, 19.8 mg/dL (median), month 2, 10.6 mg/dL; month 4, 8.7 mg/dL; and month 6, 7.1 mg/dL (P < 0.001, Friedman). Other lipid changes induced by nandrolone decanoate were an increase in the concentrations of apolipoprotein B (P < 0.02, ANOVA) and triglyceride (P = NS, ANOVA) and a decrease of high-density lipoprotein (HDL) cholesterol (P < 0.001, ANOVA) and apolipoprotein A-I (P = NS, ANOVA). The decrease in HDL cholesterol was at the expense of the HDL2 cholesterol subfraction, whereas HDL3 remained unchanged. These lipid modifications were reversible; 4 months after nandrolone decanoate withdrawal, the lipid concentrations were similar to the basal values. The changes in Lp(a) levels did not correlate with those of hemoglobin or the other lipid parameters, suggesting that the underlying mechanisms are unrelated. Our findings could be clinically relevant if confirmed by further studies.

Aged↗

Formation of N-(hexanoyl)ethanolamine, a novel phosphatidylethanolamine adduct, during the oxidation of erythrocyte membrane and low-density lipoprotein.

The primary amino groups of biomolecules such as aminophospholipids, as well as proteins, are the potential targets of covalent modifications by lipid peroxidation products; however, little attention has been paid to the modification of aminophospholipids such as phosphatidylethanolamine (PE). The purpose of this study is to characterize the formation of a novel modified phospholipid, N-(hexanoyl)phosphatidylethanolamine (HEPE), in the reaction of PE with lipid hydroperoxides using mass spectrometric analyses. Upon reaction of egg PE with 13-hydroperoxyoctadecadienoic acid or other oxidized polyunsaturated fatty acids followed by phospholipase D-mediated hydrolysis, the formation of N-(hexanoyl)ethanolamine (HEEA), a head group of HEPE, was confirmed by isotope dilution liquid chromatography/tandem mass spectrometry. Moreover, increasing HEEA was detected in the hydrolysates of oxidized erythrocyte ghosts and low-density lipoprotein with their increasing lipid peroxidation levels. Collectively, these results suggest that the N-hexanoylated product of phospholipid, HEPE, can be generated during lipid peroxidation and may serve as one mechanism for the covalent modification of aminophospholipids in vivo.

Erythrocyte Membrane↗

Formation of N-(hexanoyl)ethanolamine, a novel phosphatidylethanolamine adduct, during the oxidation of erythrocyte membrane and low-density lipoprotein.

The primary amino groups of biomolecules such as aminophospholipids, as well as proteins, are the potential targets of covalent modifications by lipid peroxidation products; however, little attention has been paid to the modification of aminophospholipids such as phosphatidylethanolamine (PE). The purpose of this study was to characterize the formation of a novel modified phospholipid, N-(hexanoyl)phosphatidylethanolamine (HEPE), in the reaction of PE with lipid hydroperoxides using mass spectrometric analyses. Upon reaction of egg PE with 13-hydroperoxyoctadecadienoic acid or other oxidized polyunsaturated fatty acids followed by phospholipase D-mediated hydrolysis, the formation of N-(hexanoyl)ethanolamine (HEEA), a head group of HEPE, was confirmed by isotope dilution liquid chromatography/tandem mass spectrometry. Moreover, increasing HEEA was detected in the hydrolysates of oxidized erythrocyte ghosts and low-density lipoprotein with their increasing lipid peroxidation levels. Collectively, these results suggest that the N-hexanoylated product of phospholipid, HEPE, can be generated during lipid peroxidation and may serve as one mechanism for the covalent modification of aminophospholipids in vivo.

Animals↗

Inhibitory effects of aromatic herbs on lipid peroxidation and protein oxidative modification of mice brain homogenate by copper in vitro.

Several aromatic herbs were inferred to have inhibitory effects on the generation of oxygen free radicals. It has been demonstrated that free radicals produced by copper produce lipid peroxidation and protein oxidative modification in the brain. The results presented here showed that several aromatic herbs, Caryophylli flos, Cinnamomi cortex, Foeniculi fructus and Zedoariae rhizoma, have inhibitory effects on lipid peroxidation or protein oxidative modification of mice brain homogenate produced by copper in vitro.

Animals↗

Alteration of arachidonate levels in tick salivary glands by dietary modification of host blood lipids.

Tick saliva contains prostaglandins of the 2-series, believed to facilitate bloodmeal acquisition. Because ticks cannot synthesize the prostaglandin precursor, arachidonic acid, investigations were undertaken to study the uptake, incorporation, and distribution of arachidonic acid in the salivary glands of the lone star tick in vitro and in vivo. Uptake of [3H]arachidonate by isolated salivary glands was reduced in the presence of low concentrations of arachidonic or eicosapentaenoic acids, but much higher, non-physiological concentrations of oleic and linoleic acids were required to inhibit [3H]arachidonate uptake. The incorporation of [3H]arachidonate into triglycerides increased at high concentrations of arachidonic or eicosapentaenoic acid, but not at any concentration of oleic or linoleic acid. Eicosatetraynoic acid greatly inhibited [3H]arachidonic acid. Guinea pigs fed hydrogenated coconut oil, safflower/primrose oil, or fish oil exhibited altered blood lipids; notably increased levels of eicosapentaenoic acid when fed fish oil. Salivary gland lipids in ticks fed on these hosts were also altered. Ticks parasitizing fish oil-fed guinea pigs contained high levels of eicosapentaenoic acid with a 30% reduction in arachidonate levels. The results demonstrated that eicosapentaenoic acid in the host diet had profound effects on arachidonate assimilation by tick salivary glands, which could lead to altered prostaglandin content in tick saliva.

Animals↗

pH-induced modifications to stratum corneum lipids investigated using thermal, spectroscopic, and chromatographic techniques.

The effects of nonphysiological pH on stratum corneum lipid content and structure have been studied. Human stratum corneum samples were soaked in solutions at pH 1, 2, 6, 11, or 12 for up to 24 h. After removal of the stratum corneum, the buffer solutions were analyzed for lipid composition using thin-layer chromatography analysis and the stratum corneum sheets were examined using differential scanning calorimetry (DSC) and Fourier transform infrared (FTIR) spectroscopy. The results demonstrate that only buffers of pH 11 or higher affect the stratum corneum lipids. No large difference in the contents of ceramides and cholesterol extracted by buffers of varying pH was observed. In contrast, free fatty acid extraction was pH dependent; amounts removed by 24-h treatment with pH 11 or 12 buffers were comparable, and were similar to amounts extracted with a methanol-chloroform mixture for 15 min. No appreciable changes in DSC and FTIR spectra were detected between untreated stratum corneum and stratum corneum samples treated with buffers at pHs in the range 1-6. For tissue treated with pH 11 and 12, the position of the endothermal melting peak T2 shifted from 72 to 74 degrees C on the DSC thermograms. Small changes in the broadness of spectral peaks at 2855 cm(-1) [attributable to upsilon(CH(2)) stretching of stratum corneum lipids and 1655 cm(-1) upsilon(C=O) stretching amide I band] can be seen in the FTIR spectra from the treated stratum corneum samples, although no shifts in peak positions were observed. Intensity changes in peaks from extraneous lipids [upsilon(C=O) stretching mode at 1735 cm(-1)] were observed after buffer treatments. The changes provoked by the alkaline buffers are not dramatic and it may be concluded that the stratum corneum appears remarkably resilient to extended exposure in both highly acidic (pH 1) and highly alkaline (pH 12) environments.

Adult↗

Lipid-protein interactions in membranes: effect of lipid composition on mobility of spin-labeled cysteine residues in yeast plasma membrane.

In order to gain direct evidence for lipid-dependent protein conformation in membrane, effects of modification of lipid composition on mobility of spin-labeled cysteine residues were investigated in the plasma membrane of the yeast Saccharomyces cerevisiae. Conversion of the bulk of phospholipids to diglycerides by treatment of the membrane with phospholipase C substantially enhanced spectral anisotropy. However, alterations of the viscosity of the lipid-bilayer by enriching the membrane with palmitelaidic or oleic acid had no effect on mobility of spin-labeled cysteine residues. These observations indicate that while the spin-labeled residues are not in direct contact with the lipid core of the membrane, there are lipid-protein interactions to the extent that removal of the polar portion of the bulk of phospholipids induces conformational changes in proteins, which in turn restrict mobility of these residues. It is concluded that conformation of membrane proteins on lipid structure and that phospholipids have a role in preserving the native conformation of proteins.

Adenosine Triphosphatases↗

Modification of liver microsomal lipids by halothane metabolites; a multi nuclear NMR spectroscopic study.

N-trifluoroacetyl phosphatidyl ethanolamine was found as an intermediate of biotransformation of halothane after intense in vivo exposure of non-induced and phenobarbital induced rabbits. The metabolite has been identified in detergent treated liver microsomes by 31P-NMR-spectroscopy and in microsomal lipid extracts by 19F-NMR- and 1H-NMR-spectroscopy as well as by thin layer chromatography. The same exposure changed phospholipid composition of liver microsomal membranes: most prominent was a substantial decrease of the ratio of phosphatidyl ethanolamines to phosphatidylcholines.

Animals↗

Modification of cell membrane lipids in Micrococcus lysodeikticus induced by pantoyl lactone.

Growth of Microccoccus lysodeikticus in the presence of pantoyl lactone brings about both qualitative and quantitative changes in cell membrane lipids. Significant amounts of the two major phospholipids (phosphatidylglycerol and diphosphatidylglycerol) are converted to lyso forms; the largest conversion occurs in the phosphatidylglycerol. In addition, amounts of several phospholipid fatty acids are changed. Physical alteration of the call membrane can be demonstrated using differential scanning calorimetry. Although growth and transport are significantly inhibited when pantoyl lactone is present, cells possessing altered call membrane phospholipds and phospholipid fatty acids, brought about by growth in the presence of pantoyl lactone, transport D-alanine, L-glutamic and L-aspartic acid normally when washed free of the pantoyl lactone.

4-Butyrolactone↗

Modification of liver mitochondrial lipids and of adenine nucleotide translocase and oxidative phosphorylation by cold adaptation.

The decrease in respiration rate following thyroidectomy is preceded by changes in the lipid composition of the mitochondrial membrane (Hoch, F.L., Subramanian, C., Dhopeshwarkar, G.A. and Mead, J.F. (1981) Lipids 16, 328-334) and in concert, changes in the kinetic parameters of the adenine nucleotide translocase (Mak, I.T., Shrago, E. and Elson, C.E. (1981) Fed. Proc. 40, 398). To demonstrate that physiological adaptation also involves this sequence of events, rats were housed at 8 degrees C for 3-4 weeks. Cold adaptation resulted in a modest (5%) increase in the unsaturation index for the mitochondrial fatty acids comprised of a significant increase in arachidonic acid and a reciprocal decrease in linoleic acid. Phospholipid analysis indicated that cold adaptation increased the mitochondrial phosphatidylethanolamine and reciprocally decreased the phosphatidylcholine content. Concomitantly, cold adaptation resulted in 25-30% increases in rat liver mitochondrial respiratory activities without changing the respiratory control or ADP/O ratios. The kinetic parameters of the adenine nucleotide translocase were determined by the back-exchange method (Pfaff, E. and Klingenberg, M. (1968) Eur. J. Biochem. 6, 66-79). At 0-4 and 10 degrees C, the Vmax and Km of the cold-adapted rat liver adenine nucleotide translocase were not distinguishable from the control values. The Ki values determined by Dixon plot studies for atractylate and palmitoyl-CoA were also comparable between the two groups. However, at 25 and 37 degrees C, cold-adapted rat liver adenine nucleotide translocase exhibited a 20% increase in Vmax and a 20% decrease in Km for external ADP. The results suggest that one adaption to a cold environment involves hormone-mediated changes in the lipid composition in the mitochondrial membranes which in turn modulate the adenine nucleotide translocase and subsequent respiratory activities.

Acclimatization↗

Studies on tetrahymena membranes. Modification of surface membrane lipids by replacement of tetrahymanol by exogenous ergosterol in Tetrahymena pyriformis.

Tetrahymena pyriformis WH-14 cells were grown in the medium supplemented with ergosterol (1 mg/100 ml) and the effects of replacement of tetrahymanol by ergosterol upon the lipid composition in the surface membranes (cilia and pellicles) were examined. 1. By scanning and freeze-etch electron microscopy it was suggested that exogenous ergosterol would be inserted into the lipid regions in the surface membranes. Although freeze-etched faces of filipin-treated membranes containing the native tetrahymanol showed a random distribution of 85-a protein particles, the ergosterol-replaced membranes after the same polyene treatment revealed the marked ultrastructural alterations on the fracture faces. 2. The replacement of tetrahymanol in membranes by ergosterol induced a profound alteration in the phospholipid class composition and a marked increase in phosphatidylethanolamine with a compensatory decrease in phosphatidylcholine and 2-aminoethylphosphonolipid. 3. There are significant and quantitative but not qualitative changes in the fatty acid composition of total lipids from the ergosterol-replaced membranes. There are also increases in saturated and decreases in unsaturated fatty acids. Phosphatidylethanolamine acyl chains particularly become more saturated, as compared with two other phospholipids, in ergosterol-replaced pellicles. This increase in saturation is due to an appreciable increase in C14:0, C16:0 and iso-C17:0, and a decrease in C18:1(delta9), C18:2(delta9,12) and C18:3(delta6,9,12). 4. These results suggest that profound alterations in phospholipids as well as in their fatty acyl chains are required to modify the overall membrane lipid composition for the maintenance of proper membrane fluidity. Our data would also support the thesis that polat head groups are involved in the membrane lipid organization and that sterols interact selectively with phospholipid molecules containing the appropriate fatty acyl chain composition in biological membranes.

Acetates↗

Effect of age on the modification of rat plasma lipids by fish and soybean oil diets.

The effects of sardine and soybean oils on plasma lipids have been studied in young and aged rats. Plasma cholesterol and bile acids of aged rats fed on a sardine oil diet decreased to a greater degree than those of young rats. Cholesterol, bile acids and phospholipids of the soybean oil diet group decreased only in aged rats. Increases in plasma eicosapentaenoic (sardine) and linoleic (soybean) acid levels of aged rats were observed to be greater than those of young rats. These results indicate that the age enhances the effects of fish and soybean oils on plasma lipids by suppressing their characteristic fatty acid metabolism.

Aging↗

Modification of erythrocyte membrane lipid composition induced by a single intravenous infusion of phospholipid-triacylglycerol emulsions in man.

The study aimed to investigate whether, during short term infusion of lipid emulsions in man, red blood cell (RBC) membrane lipid composition was altered and RBC-free cholesterol (FC) could serve as a source of FC accumulated in the plasma. 3 normal subjects were infused intravenously with either 10% Intralipid [10% IL; PL:triglyceride (TG) weight ratio of 0.12] at the rates of 0.1, 0.2 and 0.3 g TG.kg(-1).h(-1) (providing PL intakes of 12, 24, 36 mg.kg(-1).h(-1), respectively) or with 30% Intralipid (30% IL; PL:TG ratio of 0.04) at the rate of 0.3 g TG.kg(-1).h(-1) (providing 12 mg PL.kg(-1).h(-1)). Infusion of 10% IL at a slow rate and 30% IL at a high rate caused no change in RBC and plasma FC content. However, 10% IL infusion at intermediate and high rates induced a significant decrease in RBC-FC: PL ratio. This change was still present at 18 h after the cessation of high rate infusion. RBC-FC: PL ratio and plasma PL measured during infusion were significantly correlated (r = -0.87, p < 0.001). FC efflux from RBC appears to contribute to the rise in plasma FC. This study indicates that the excessive amount of PL present as liposomes in some intravenous lipid emulsions can alter erythrocyte membrane lipid composition.

Journal Article↗

Biological optimization of hyperthermia: modification of tumor membrane lipids.

The sensitivity of the solid mammary adenocarcinomas CA755 and MtGB, grown in the medial aspect of the hind legs of host mice, to local hyperthermia (43.5 +/- 0.1 degrees C for 1 hr) was increased by feeding the host mice a diet enriched in linoleic acid. The enhanced sensitivity was expressed only when the diet was fed for 15 days prior to the tumor transfer. Infusion of lidocaine into the tumor immediately before the hyperthermic exposure enhanced the thermal sensitivity of the controls but not of the linoleic acid-enriched tumors. Sensitivity was analyzed by tumor growth rates and growth delay following exposure. The fatty acid patterns revealed that the proportion of polyunsaturated fatty acids (20:4 and 22:6) decreased reciprocally with increased linoleic acid in the liver phospholipids, whereas in the tumor all polyunsaturated fatty acids increased at the expense of monounsaturated fatty acids. These studies suggest that dietary lipids affected tumor cell sensitivity to hyperthermia.

Adenocarcinoma↗