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PubMed1995

The interaction between protein kinase C and lipid cofactors studied by simultaneous observation of lipid and protein fluorescence.

The interaction of protein kinase C (PKC) with lipids was probed by a dual approach. Pyrene-labeled lipid analogues of diacylglycerol, phosphatidylserine (PS), phosphatidylinositol (PI), phosphatidylinositol 4-phosphate (PIP), and phosphatidylcholine (PC) were used both as acceptors of tryptophan excitation energy of PKC and as membrane probes for intra- and intermolecular lipid chain collisions by measuring the ratio of excimer-to-monomer fluorescence intensity (EM). Both in micelles of polyoxyethylene 9-lauryl ether and in dioleoyl-PC vesicles, interaction of PKC with monopyrenyl PS (pyr-PS) in the absence of calcium resulted in a relatively slow decrease of the EM value. This effect on the lipid dynamics was accompanied by quenching of the tryptophan fluorescence of PKC. Addition of calcium resulted in a rapid further decrease of the EM ratio of pyr-PS and in additional quenching of the tryptophan fluorescence. When 4 mol % of pyr-PS was replaced by 0.5 mol % of dipyrenyl-labeled diacylglycerol a decrease of the intramolecular excimer formation rate and tryptophan fluorescence could only be detected in the presence of calcium and PS. Strong binding was also observed with dipyrenyl-labeled PIP (dipyr-PIP), but not with the other dipyrenyl-labeled lipids: PI, PS, or PC. In addition, the EM ratios of dipyr-PIP were not affected by phorbol 12-myristate 13-acetate, indicating that phorbol 12-myristate 13-acetate and dipyr-PIP can bind simultaneously to PKC.

Binding, Competitive↗
PubMed2002

Final report on the safety assessment of human placental protein, hydrolyzed human placental protein, human placental enzymes, human placental lipids, human umbilical extract, placental protein, hydrolyzed placental protein, placental enzymes, placental lipids, and umbilical extract.

Various proteins, lipids, or other extracts from human or other animal placentas are described as cosmetic ingredients. Human Placental Protein comprises protein derived from human placentas. Placental Protein is derived from animal placentas. Similarly, Human Placental Lipids and Placental Lipids are the lipid fractions from the same source materials. Hydrolyzed Human Placental Protein and Hydrolyzed Placental Protein are produced from the respective protein extracts by acid, enzyme, or other hydrolysis methods. Human Placental Enzymes and Placental Enzymes are enzymes obtained by aqueous extraction of human or other animal placental material. Human Umbilical Extract and Umbilical Extract are unspecified extracts of material from human or other animal umbilical cords. Different materials called Human Placental Extracts and Placental Extracts, assumed to contain estrogenic hormones or other biologically active substances, are not recognized as cosmetic ingredients, even though the use of these ingredients in cosmetics have been reported to the Food and Drug Administration (FDA). Human-derived ingredients are prohibited from use under the provisions of the European Union cosmetics directive based on concerns about transmission of human spongiform encephalopathies and viral diseases, for example, human immunodeficiency virus (HIV). Umbilical Extract has precedent for unrestricted use in Japan, except for certain products. Most of these ingredients are described as hair-conditioning agents and miscellaneous skin-conditioning agents, although the umbilical extracts function as biological additives in cosmetics. Of the human-derived ingredients, only Human Placental Protein is currently reported to be used. Animal-derived placental proteins, hydrolyzed proteins, lipids, and enzymes were all currently reported to be used. No current uses of the umbilical extracts were reported. Most of the available data relates to placental derivatives that appear to have estrogenic or other biological activity. The one clinical study that appears to utilize proteinaceous material only reported no irritant reaction. Clearly, the available data are insufficient to support safety of these ingredients in cosmetics. The additional data needed include (1) skin sensitization at concentration of use; (2) gross pathology and histopathology in skin and other major organ systems associated with repeated exposures, and dermal reproductive and developmental toxicity data; (3) photosensitization; (4) one genotoxicity assay in a mammalian system; if positive, then a 2-year dermal carcinogenicity study using National Toxicology Program (NTP) methods may be needed; (5) ocular toxicity, if available. Any studies should be done on all ingredients unless chemical analysis data show similarity among ingredients. Because there is confusion and concern about the use of substances with estrogenic or other biological activity in cosmetic formulations, it was concluded that none of these ingredients used in cosmetics should deliver any metabolic/endocrine activity. In addition, any current use of these ingredients should be free of detectable pathogenic viruses or infectious agents.

Animals↗
PubMed2003

Rapid communication: partitioning of persistent lipophilic compounds, including dioxins, between human milk lipid and blood lipid: an initial assessment.

A systematic program of sampling and analysis of blood serum for dioxins, furans, and dioxinlike polychlorinated biphenyls (PCBs) has been initiated in the United States through the National Health and Nutrition Examination Survey (NHANES) program. While such data could potentially be used to estimate population-level changes in human milk lipid concentrations of chemicals, such estimates would depend on understanding the relationship between human blood lipid and milk lipid concentrations of the compounds of interest. For dioxins and furans, extremely limited data in humans currently exist for paired blood/milk samples. These data reviewed in this article, support the hypothesis that, over a population and across time, human milk lipid levels of these compounds generally reflect blood lipid levels. However, these data also suggest that significant variations in these ratios are possible among individuals and at various times.

Dioxins↗
PubMed2004

Molecular biology and immunology for clinicians 29: lipid domains, lipid rafts, and caveolae.

The development of an antigen-specific immune response depends on the peptide-loaded MHC molecule on the surface of the antigen-presenting cell being found by the antigen-specific receptor on the cell about to be activated (the T-cell antigen receptor for T-cells or the membrane-bound immunoglobulin molecule on B-cells). The details of this process are becoming clear now with the appreciation of the supramolecular organization of the structures that make this cell-cell interaction. In the last 6 years has come an appreciation of the heterogeneity of the lipid bilayer membrane (a concept first put forth over 20 years ago), with certain lipids and membrane-bound proteins segregating into discrete ships called "lipid rafts" sailing in the surrounding more liquid lipid bilayer membrane. Knowledge of these microscopic structures leads to a better understanding of how antigen-specific responses are triggered and how aberrant responses are avoided; as one leader in the field put it, "keeping T-cells rested but ready."Membrane heterogeneity directly contributes to the rapid development of a more formalized cell-cell interaction that has been termed the "immunologic synapse." It is at this synapse that the acquired immune response, antigen specificity, is learned. In addition to antigen presentation, lipid rafts have also been implicated in signaling through a large number of receptors, endocytosis, cell interactions with pathogens and toxins, budding of viruses from host cell membrane, and the pathogenesis of prion disorders. Yet again, an insight in one discrete field of cell biology is proving to be of great relevance in a host of other areas of study.

Journal Article↗
PubMed1991

Familial aggregation of lipids and lipoproteins in families ascertained through random and nonrandom probands in the Iowa Lipid Research Clinics family study.

The aggregation of lipids [total cholesterol (CH) and triglyceride (TG)] and lipoproteins [high-density lipoprotein cholesterol (HDL) and low-density lipoprotein cholesterol (LDL)] in families ascertained through random and nonrandom probands in the Iowa Lipid Research Clinics family study was examined. Nonrandom probands were selected because their lipid levels (at a prior screening visit) exceeded a certain pre-specified threshold. The statistical method conditions the likelihood function on the actual event that the proband's value is beyond the threshold. This method allows for estimation of the path model parameters in randomly and nonrandomly ascertained families jointly and separately, thus enabling tests of heterogeneity between the two types of samples. Marked heterogeneity between the random and the hyperlipidemic samples is detected in the multifactorial transmission for TG and HDL, and moderate heterogeneity is detected for CH and LDL, with a pattern of higher genetic heritability estimates in the random than nonrandom samples. The observed pattern of heterogeneity is compatible with a higher prevalence in the random sample of certain dyslipoproteinemias that are associated with nonelevated lipids. For the random samples, genetic heritabilities are higher for CH and HDL (about 60%) than for TG and LDL (about 50%). For the nonrandom samples those estimates are about 45, 40, 35 and 30% for HDL, CH, LDL and TG, respectively. Little to no cultural (familial environmental) heritability is evident for CH and LDL, although 10-20% of the phenotypic variance is due to cultural factors for TG and HDL. These results suggest that the etiologies for lipids and lipoproteins may be quite different in random versus hyperlipidemic samples.

Adult↗
PubMed1975

Lipid metabolism in pregnancy. II. Altered lipid composition in intermediage, very low, low and high-density lipoprotein fractions.

The hyperlipidemia of pregnancy consists primarily of an increase in triglyceride with lesser rises in cholesterol and phospholipid. As a further characterization, we have analyzed all lipids in the major lipoprotein subfractions in fasting pregnant and non-pregnant women. An elevated triglyceride in the major lipoprotein fractions in pregnancy is confirmed. The triglyceride rises in VLDL and IDL (density 1.006-1.019 lipoprotein) are associated with proportional rises in cholesterol and phospholipid. The result is a 3-4-fold increase of compositionally unchanged lipoprotein lipid. Contrasting changes are seen in LDL, density 1.019-1.063 lipoprotein, and HDL. In these fractions, triglyceride rises more than cholesterol and phospholipid. As a result, an increase in triglyceride on a percentage basis tends to reduce the contribution of the other two lipids. Nonetheless, on an absolute basis HDL cholesterol is not significantly reduced. The proportional increases in all lipids of VLDL and IDL fractions are consistent with increased VLDL production in pregnancy as suggested by data from animal systems. However, alterations in removal are not rules out. Maintenance of the HDL cholesterol level distinguishes pregnancy from other endogenous hypertriglyceridemias where HDL cholesterol is reduced. One may speculate that these physiological adaptations in material lipid transport can serve the increased energy needs of the mother, supply steroid hormone precursors for the placenta, and provide cholesterol and essential fatty acids for the fetus.

Cholesterol↗
PubMed2005

Large-scale cohort study on the relationship between serum lipid concentrations and risk of cerebrovascular disease under low-dose simvastatin in Japanese patients with hypercholesterolemia: sub-analysis of the Japan Lipid Intervention Trial (J-LIT).

BACKGROUND: The Japan Lipid Intervention Trial was a nationwide cohort study of 52,421 hypercholesterolemic patients treated with open-labeled simvastatin for 6 years under standard clinical practices. Cerebrovascular disease (CVD) is one of the leading causes of death in Japan, but the effect of hypercholesterolemia on CVD has not been well established in Japanese patients. This study aimed to determine the relationship between the risk of CVD and serum lipid concentrations during treatment in Japan. METHODS AND RESULTS: Patients were treated with 5-10 mg/day of simvastatin and all, including those who discontinued simvastatin for any reason, had their lipid concentrations and incidence of CVD monitored for 6 years. Data of 41,088 patients were analyzed in this study, excluding those who had a history of coronary heart disease or CVD. The risk of cerebral infarction was higher in patients whose mean total cholesterol concentrations during treatment were > or = 240 mg/dl, low-density lipoprotein cholesterol concentrations > or = 160 mg/dl, triglycerides > or = 150 mg/dl and high-density lipoprotein cholesterol concentrations <40 mg/dl. There was no obvious correlation between cerebral hemorrhage and serum lipid concentrations. CONCLUSION: Improvement of serum lipid concentrations is important for reducing the incidence of cerebral infarction.

Cerebral Infarction↗
PubMed2003

Effects of highly purified structured lipids containing medium-chain fatty acids and linoleic acid on lipid profiles in rats.

The purpose of this study is to examine the effects of highly purified structured lipids on serum and liver lipid profiles in rats. We also investigated in vitro hydrolysis of lipid emulsions by porcine pancreas. Hydrolysis rates of medium chain (M)-linoleic (L)-medium chain (M) types were 2 to 3 times higher than those of L-M-L types. The diet containing structured lipids or corn oil was administered to rats for 4 weeks. There were no significant differences in growth and food efficiency. Serum cholesterol levels were significantly lower (P<0.05) in the 2-octanoyl-1,3-dilinoleoyl-glycerol, 2-linoleoyl-1,3-didecanoyl-glycerol, and 2-decanoyl-1,3-dilinoleoyl-glycerol groups than in the corn-oil group. Serum triglyceride levels were significantly lower (P<0.05) in rats fed L-M-L types than those in the other groups. Serum non-esterified fatty acid (NEFA) and beta-hydroxybutylate levels were significantly higher (P<0.01) in rats fed M-L-M types than those of the other groups. These results indicate that the feeding of highly purified L-M-L types could effectively improve serum and liver lipid profiles and that M-L-M types may be a preferable substrate for the pancreas and contribute to energy supply in rats.

3-Hydroxybutyric Acid↗
PubMed2005

Lipid alterations in the earliest clinically recognizable stage of Alzheimer's disease: implication of the role of lipids in the pathogenesis of Alzheimer's disease.

Lipids have many important yet distinct functions in cellular homeostasis such as forming an impermeable barrier separating intracellular and extracellular compartments, providing a matrix for the appropriate interactions of membrane-associated proteins, and serving as storage reservoirs for biologically active second messengers. Alterations in cellular lipids may therefore result in abnormal cellular functions. This review summarizes the results from the examination of lipid alterations in Alzheimer's disease (AD). In addition to the effects of cholesterol on AD, substantial depletions of plasmalogen and sulfatide as well as dramatic increases in ceramide are specifically manifested at the earliest clinically recognizable stage of AD. The potential mechanism(s) underlying these changes and the potential consequences of these changes in neuronal function and in AD development are also discussed. Collectively, this review will provide an overview of the lipid alterations in Alzheimer's disease and the relationship of these lipid alterations with the development of AD pathogenesis.

Alzheimer Disease↗
PubMed2002

Fine specificity of TCR complementarity-determining region residues and lipid antigen hydrophilic moieties in the recognition of a CD1-lipid complex.

alphabeta TCR can recognize peptides presented by MHC molecules or lipids and glycolipids presented by CD1 proteins. Whereas the structural basis for peptide/MHC recognition is now clearly understood, it is not known how the TCR can interact with such disparate molecules as lipids. Recently, we demonstrated that the alphabeta TCR confers specificity for both the lipid Ag and CD1 isoform restriction, indicating that the TCR is likely to recognize a lipid/CD1 complex. We hypothesized that lipids may bind to CD1 via their hydrophobic alkyl and acyl chains, exposing the hydrophilic sugar, phosphate, and other polar functions for interaction with the TCR complementarity-determining regions (CDRs). To test this model, we mutated the residues in the CDR3 region of the DN1 TCR beta-chain that were predicted to project between the CD1b alpha helices in a model of the TCR/CD1 complex. In addition, we tested the requirement for the negatively charged and polar functions of mycolic acid for Ag recognition. Our findings indicate that the CDR loops of the TCR form the Ag recognition domain of CD1-restricted TCRs and suggest that the hydrophilic domains of a lipid Ag can form a combinatorial epitope recognized by the TCR.

Amino Acid Sequence↗
PubMed2005

Cost-effectiveness of lipid-lowering treatment according to lipid level.

BACKGROUND: Recent studies suggest that the benefit of lipid-lowering treatment for the primary and secondary prevention of cardiovascular disease (CVD) extends to individuals with average cholesterol levels, to women and to the elderly. However, the proportion of the general population for which treatment is cost-effective has not been evaluated. OBJECTIVES AND METHODS: Using data provided by the Canadian Heart Health Survey, the level of CVD risk was estimated for a random sample of the total population. A cost-effectiveness ratio for simvastatin was then calculated for each individual in the sample. Lastly, the proportion of the total population for which lipid-lowering therapy would be cost-effective for primary and secondary prevention of CVD was estimated according to total cholesterol (TC) levels. RESULTS: Among the surveyed individuals who were 30 to 74 years of age, 2212 had CVD and 12,982 did not. Among those with a TC level higher than 6.2 mmol/L, the proportions of individuals for which lipid-lowering therapy was cost-effective (at a level of less than 50,000 dollars per year of life saved) were 85.6% of men and 28.7% of women for primary prevention, and 99.8% of men and 86.1% of women for secondary prevention. The estimated cost of one year of lipid-lowering treatment for all individuals in the population with a TC level higher than 6.2 mmol/L and for all individuals regardless of TC levels for whom treatment would be cost-effective was $1 billion and 3.9 billion dollars, respectively. CONCLUSIONS: Lipid-lowering treatment for CVD prevention is cost-effective for a high proportion of the population, even for primary prevention. As a result, the cost of population-wide treatment for only one year is high even among individuals with a TC level higher than 6.2 mmol/L. Such costs should be considered in health care policy decisions.

Adult↗
PubMedDate not supplied

Keratinocyte lipid fluidity under the influence of cholesterols, hydrocortisones, "active lipid", tocopherol and retinoic acid--a fluorescence polarization study with regard to physiological and pathophysiological epidermopoiesis and its therapeutic accessibility.

Lipid fluidity of freshly isolated human (H) and guinea pig (GP) keratinocytes (K) was determined as the reciprocal of diphenylhexatriene (DPH) fluorescence polarization (P-value), the temperature being kept at 25 degrees C and cell density standardized to 550,000 per ml (level of statistical significance a less than 0.05). An experimental model involving short-term incubations (2.5 hours, 37 degrees C) of GPK in 1% ethanolic lipid solutions (15 mg lipid agent per ml ethanol) was set up to investigate accumulation a) of cholesterol due to terminal differentiation of keratinocytes and b) of cholesteryl sulfate due to the lack of steroid sulfatase activity in recessive X-linked ichthyosis (RXLI). In comparison to the control including 1% ethanol (P = 0.291 +/- 0.004), significant rigidifying effects were demonstrated for cholesteryl hemisuccinate (0.331 +/- 0.005) and cholesteryl sulfate (0.310 +/- 0.002). Correspondingly, a significant increase of the P-value was also induced by cholesteryl hemisuccinate in HK. Rigidification of GPK by a preincubation with cholesteryl sulfate (P = 0.306 +/- 0.002) could be antagonized by a subsequent short-term incubation with "active lipid (mixture 721)" (0.285 +/- 0.003, a less than 0.05) which may be relevant for future therapeutic strategies in RXLI. Other steran molecules such as hydrocortisone-21-hemisuccinate or hydrocortisone acetate did not affect lipid fluidity. With regard to the therapeutic potency of retinoids in epidermopoietic disorders, incubations of HK with all-trans-retinoic-acid were compared to those with also lipophilic vitamin E, i.e. d-alpha-tocopherol, for 2.5 hours at 37 degrees C using 1% DMSO as a solvent.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Effect of smoking on the lipid composition of lung lining fluid and relationship between immunostimulatory lipids, inflammatory cells and foamy macrophages in extrinsic allergic alveolitis.

Normal lung lining fluid suppresses lymphoproliferative responses. This effect is mediated by the major phospholipid components, but minor lipid components can stimulate lymphocyte proliferation. The aim of this study was to discover whether the changes in lung lipid composition reported in patients with extrinsic allergic alveolitis (EAA) might influence the levels of lymphocytes which occur in the lungs of these patients. Since cigarette smokers are less susceptible to EAA, we also investigated the effect of smoking on the lipid composition of lung lining fluid. Lung lining fluid was sampled by bronchoalveolar lavage (BAL) from 15 patients with EAA, and 9 non-smokers and 13 smokers without lung disease. The smoking controls had increases in phosphatidylethanolamine, sphingomyelin and phosphatidylglycerol, but lower levels of cholesterol and cholesterol:total phospholipid ratios compared with the nonsmoking controls. By contrast, the patients with EAA had increases in total phospholipid and sphingomyelin; there were no smoking related decreases in cholesterol; and several patients had levels of cholesterol and cholesterol:total phospholipid ratios above the upper limit for the controls. In the BAL fluids of the EAA patients, the levels.ml-1 of the immunostimulatory lipids sphingomyelin, phosphatidylethanolamine, cholesterol and cholesterol esters correlated with the number.ml-1 of lymphocytes, mast cells, neutrophils and "foamy" macrophages. Cholesterol levels (rs = 0.82) and lymphocyte counts (rs = 0.90) correlated most closely with "foamy" macrophages (p less than 0.001), suggesting that uptake of cholesterol by macrophages may enhance antigen-presenting function. These observations provide some support for the hypothesis that inflammatory reactions in the lungs might be influenced by the local lipid environment.

Adult↗
PubMed1989

Lipid-lipid interactions as regulators of carboxylester lipase activity.

The hydrolysis of 1,3-dioleoylglycerol and related substrates by mammalian pancreatic carboxylester lipases was studied. Mixed lipid films of substrates with 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine at the argon-buffer interface were exposed to relatively high levels of monomeric porcine pancreatic carboxylester lipase for a brief period. With either 1,3-dioleoylglycerol, 1,2-dioleoylglycerol, trioleoylglycerol, or oleoylmethanol as a substrate, the percentage of substrate hydrolysis increased abruptly from near zero to near 100% with increasing proportion of substrate in the film. The phospholipid was not hydrolyzed. Using 1,3-dioleoylglycerol as the substrate with either the dimeric, porcine pancreatic carboxylester lipase, human pancreatic carboxylester lipase, or human milk bile salt-stimulated lipase gave results identical to those obtained with the porcine monomer. Hydrolysis of 1,3-dioleoylglycerol by porcine monomeric carboxylester lipase was independent of the initial surface pressure of the film. However, a strong correlation was observed between hydrolysis and interfacial lipid composition at all surface pressures, even if bulk 1,3-dioleoylglycerol was also present. The ultrasensitive dependence of hydrolysis on interfacial lipid composition, i.e. lipid-lipid interactions, suggests that such "switching" may contribute to the regulation of diacylglycerol levels in cells where they function in signal transduction.

Animals↗
PubMed1982

[Existence of boundary lipids in reconstituted hydrophobic protein-lipid system].

A fraction of hydrophobic proteins (9, 14, 18 kD) soluble in a chloroform-methanol mixture (2:1) has been isolated from Micrococcus lysodeikticus bacterial membranes. The proteins obtained were introduced into proteoliposomes at a protein/lipid weight ratio ranging from 0.1 to 0.25 in combination with the fluorescent probe pyrene or the spin probe 2-(14-carboxytetradecyl)-2-ethyl-4.4-dimethyl-3-oxasolidinyloxyl. The excimertization of pyrene upon direct excitation of its molecules (gamma excit.=338nm) and under conditions of energy transfer from the excited protein chromophores to pyrene (gamma excit.=286nm) and the spin-spin exchange between the spin probe molecules was investigated. The experimental results suggest that the hydrophobic protein molecules are surrounded by a structurally heterogenous lipid area containing up to 3.3 mg of lipid per l mg of protein. The maximal expression of structural heterogeneity was observed at the minimal content of protein in the proteoliposomes. Treatment with the membranotropic antibiotic gramicidin S resulted in disappearance of lateral heterogeneity of lipids in the constituted system and in lipid aggregation in bacterial membranes. It is assumed that the aggregability of membrane proteins depends on the structural rearrangement of some part of lipid bilayer around them.

Bacterial Proteins↗
PubMed1975

[Ultrastructure and morphogenesis of ceroid pigment. I. Phagocytosis and formation of lipid-containing lysosomes in Kupffer Cells after intravenous injection of unsaturated lipids (author's transl)].

Wistar rats were injected intravenously with cod liver oil emulsion. The phagocytosis of these lipids by the Kupffer cells as well as the formation of lipid-containing lysosomes were studied electron microscopically within a period of 5 min to 12 hrs. The emulsified lipids are incorporated into the cytoplasm by membrane-vesiculation. The lipid-containing phagocytic vacuoles (lipophagosomes) were transformed into secondary lysosomes (lipophagolysosomes). This change occurs in two phases. Immediately after phagocytosis the lipophagosomes are provided with lysosomal enzymes by fusion with pre-existent lysosomes (dense bodies) of the Kupffer cells. These are mainly the so-called small homogenous dense bodies which are probably primary lysosomes of the type of "storage granules". In the second phase which begins 15-30 min after the injection; the fusion of lipophagosomes with newly produced primary lysosomes within the Golgi apparatus is predominant. Therefore, the enzyme supply of the phagocytic vacuoles does not occur at once but in small amounts during a longer period. The lipids slowly change into an amorphous electron-dense mass 12 hrs after the injection. Obviously, these changes are the first step to the formation of ceroid pigment.

Acid Phosphatase↗
PubMed1998

Perinatal expression of genes that may participate in lipid metabolism by lipid-laden lung fibroblasts.

Although a morphologically distinct population of lipid-laden interstitial cells (lipofibroblasts, LF), has been identified, the origins and functions of this population during lung development and disease remain undefined. Illumination of the developmental and functional characteristics of two other populations of lipid-laden mesenchymal cells, namely adipocytes and hepatic lipocytes, has fashioned tools that can be used to explore similar properties in pulmonary LFs. As the LF is transiently a very abundant cell in the perinatal lung, we elected to study the perinatal ontogeny of the expression of several genes that are involved in the acquisition of lipids by adipocytes, and may be involved in promoting the triglyceride accumulation that is the morphologic hallmark of the pulmonary LF. We found that the maximal expression of peroxisome proliferator-activated receptor-gamma (PPAR-gamma), at gestational day 21 in the LF, precedes the rise at birth, in the expression of genes that are involved in the hydrolysis of triglycerides at the plasma membrane (lipoprotein lipase, LPL), transport of fatty acids across the plasma membrane (fatty acid transporter, FAT) and in the cytoplasm (adipocyte lipid binding protein, ALBP). The steady-state levels of LPL, FAT, and ALBP mRNAs that were isolated from whole lung tissue showed a similar temporal pattern. The levels of the protein products of the LPL and ALBP genes changed in tandem with those of their precursor mRNAs in the LF, suggesting that these gene products are under pre-translational control. These findings indicate that characteristic adipocyte genes are also expressed in lipid-laden pulmonary fibroblasts and may participate in triglyceride accumulation and metabolism by these cells.

Animals↗
PubMed2000

Abnormalities of erythrocyte membrane fluidity, lipid composition, and lipid peroxidation in systemic sclerosis: evidence of free radical-mediated injury.

OBJECTIVE: To elucidate whether oxidative injury occurs in systemic sclerosis (SSc) and whether it affects the erythrocyte membrane (EM) properties. METHODS: EM fluidity and lipid composition (cholesterol:phospholipid molar ratio [C:PL], fatty acid composition) were studied in 52 patients with SSc and in 53 subjects without SSc (32 with primary Raynaud's phenomenon [RP] and 21 healthy subjects [controls]). Fluidity was measured as the fluorescence anisotropy of the hydrophobic fluorescent probe DPH (1,6-diphenyl-1,3,5-hexatriene). Lipid peroxidation products were determined as thiobarbituric acid-reactive substances (TBARS). RESULTS: EM fluidity was significantly lower in SSc patients than in primary RP patients and controls (P < 0.001). The EM C:PL molar ratio was significantly higher in SSc patients than in primary RP patients and controls (P < 0.05). Levels of EM polyunsaturated n6 fatty acids (PUFA n6) were significantly lower in SSc patients than in primary RP patients and controls (P < 0.001). TBARS were significantly increased in SSc patients compared with primary RP patients and controls (P < 0.001). Multiple regression analyses indicated that the reduced EM fluidity was partly due to its greater C:PL molar ratio, lower PUFA n6 content, and higher TBARS levels. EM fluidity was lower among patients with nailfold capillary loss (P < 0.001) and digital ischemic ulcers (P < 0.05). EM lipid peroxidation products were higher among patients with pulmonary involvement (bibasal pulmonary fibrosis [P < 0.05] and reduced levels of diffusing capacity for carbon monoxide [P < 0.001]) and among patients who were positive for anti-topoisomerase I antibodies (P < 0.05) or negative for anticentromere antibodies (P < 0.001). CONCLUSION: Our findings support the idea that oxidative injury occurs in SSc and that, through lipid peroxidation, it induces structural and functional changes of the EM that may contribute to the development of the microvascular abnormalities that are seen in the disease.

Erythrocyte Membrane↗