Higher Levels Of Phosphatidylcholine Research Articles

Multidimensional plasma lipid composition and its causal association with type 2 diabetes mellitus: A Mendelian randomization study

Background and aimRecent research extends our knowledge of plasma lipid species, building on established links between serum lipid levels and Type 2 Diabetes Mellitus (T2DM) risk. Identifying the causal roles of these lipid species is key to improving T2DM risk assessment. Methods and resultsThis study employs Mendelian randomization (MR) to investigate the causal relationship between 179 lipid species across 13 lipid categories and T2DM. Summary-level data were sourced from genome-wide association studies. The primary analytical methods included the inverse variance weighted (IVW) approach and the Wald ratio, complemented by a series of sensitivity analyses to ensure the robustness of results. The IVW analysis reveals a significant causal association between elevated levels of ceramide (d40:2) (OR = 1.071, 95% CI 1.034–1.109, P = 1.36 × 10−4), sphingomyelin (d38:1) (OR = 1.052, 95% CI 1.028–1.077, P = 1.80 × 10−5), and triacylglycerol (56:8) (OR = 1.174, 95% CI 1.108–1.243, P = 4.65 × 10−8), and an increased risk of T2DM. Conversely, Wald ratio analysis indicates that higher levels of phosphatidylcholine (O-16:1_16:0) (OR = 0.928, 95% CI 0.892–0.966, P = 2.37 × 10−4), phosphatidylcholine (O-16:1_20:4) (OR = 0.932, 95% CI 0.897–0.967, P = 2.37 × 10−4), and phosphatidylcholine (O-18:2_20:4) (OR = 0.872, 95% CI 0.812–0.935, P = 1.24 × 10−4) are significantly associated with a reduced risk of T2DM. Furthermore, suggestive causal evidence for 22 additional lipid species was identified. ConclusionsThis MR study establishes a causal relationship between specific lipid classes in modulating the risk of T2DM. It offers new insights for risk assessment and potential therapeutic targets in T2DM.

Contrasting the phospholipid profiles of two neoplastic cell lines reveal a high PC:PE ratio for SH-SY5Y cells relative to A431 cells

Lipids have been implicated in Parkinson's Disease (PD). We therefore studied the lipid profile of the neuroblastoma SH-SY5Y cell line, which is used extensively in PD research and compared it to that of the A431 epithelial cancer cell line. We have isolated whole cell extracts (WC) and plasma membrane (PM) fractions of both cell lines. The isolates were analyzed with 31P NMR. We observed a significant higher abundance of phosphatidylcholine (PC) for SH-SY5Y cells for both WC (55 ± 4.1%) and PM (63.3 ± 3.1%) compared to WC (40.5 ± 2.2%) and PM (43.4 ± 1.3%) of A431. Moreover, a higher abundance of phosphatidylethanolamine was detected for the WC of A431 compared to the SH-SY5Y. Using LC-MS/MS, we also determined the relative abundance of fatty acid (FA) moieties for each phospholipid class, finding that SH-SY5Y had high polyunsaturated FA levels, including arachidonic acid compared to A431 cells. When comparing our results to reported compositions of brain and neural tissues, we note the much higher PC levels, as well as very low levels of docosahexaenoic acid. However, relative levels of arachidonic acid and other polyunsaturated fatty acids were elevated, in line with what is desirable for a neural model system.

Lipidomic Analyses Reveal Specific Alterations of Phosphatidylcholine in Dystrophic Mdx Muscle.

In Duchenne muscular dystrophy (DMD), lack of dystrophin increases the permeability of myofiber plasma membranes to ions and larger macromolecules, disrupting calcium signaling and leading to progressive muscle wasting. Although the biological origin and meaning are unclear, alterations of phosphatidylcholine (PC) are reported in affected skeletal muscles of patients with DMD that may include higher levels of fatty acid (FA) 18:1 chains and lower levels of FA 18:2 chains, possibly reflected in relatively high levels of PC 34:1 (with 16:0_18:1 chain sets) and low levels of PC 34:2 (with 16:0_18:2 chain sets). Similar PC alterations have been reported to occur in the mdx mouse model of DMD. However, altered ratios of PC 34:1 to PC 34:2 have been variably reported, and we also observed that PC 34:2 levels were nearly equally elevated as PC 34:1 in the affected mdx muscles. We hypothesized that experimental factors that often varied between studies; including muscle types sampled, mouse ages, and mouse diets; may strongly impact the PC alterations detected in dystrophic muscle of mdx mice, especially the PC 34:1 to PC 34:2 ratios. In order to test our hypothesis, we performed comprehensive lipidomic analyses of PC and phosphatidylethanolamine (PE) in several muscles (extensor digitorum longus, gastrocnemius, and soleus) and determined the mdx-specific alterations. The alterations in PC 34:1 and PC 34:2 were closely monitored from the neonate period to the adult, and also in mice raised on several diets that varied in their fats. PC 34:1 was naturally high in neonate’s muscle and decreased until age ∼3-weeks (disease onset age), and thereafter remained low in WT muscles but was higher in regenerated mdx muscles. Among the muscle types, soleus showed a distinctive phospholipid pattern with early and diminished mdx alterations. Diet was a major factor to impact PC 34:1/PC 34:2 ratios because mdx-specific alterations of PC 34:2 but not PC 34:1 were strictly dependent on diet. Our study identifies high PC 34:1 as a consistent biochemical feature of regenerated mdx-muscle and indicates nutritional approaches are also effective to modify the phospholipid compositions.

Pathogenicity and Lipid Composition of Mycelium of the Fungus Stagonospora cirsii VIZR 1.41 during Submerged Cultivation

In order to identify qualitative markers of a potential mycoherbicide against Canada thistle based on the mycelium of the fungus Stagonospora cirsii VIZR 1.41, changes in its pathogenicity and lipid profiles during submerged cultivation on liquid sucrose-soybean medium were analyzed. The fatty-acid composition of major lipids and the identification of molecular species of structural lipids were determined. The lipid composition during fungal growth changed together with its pathogenicity. The highly pathogenic mycelium of the fungus (at the log phase of growth) was characterized with the relatively highest content of structural lipids: phosphatidylcholine (PC), phosphatidylethanolamine (PE), and ergosterol (ES). Their relative concentration decreased with culture age and a decrease in pathogenicity. The highest lipid yield was found at the beginning of stationary growth phase (at the maximal biomass yield) of S. cirsii; triacylglycerides (TAGs) were the most abundant. The double-bond index of fatty acids in glycerolipids decreased with culture age, and the substitution of molecular PC species (34:2 versus 36:4) and PE (36:4 versus 34:2) was observed as well. High levels of ES, TAG, PC (in particular, 34:2 forms) and PE (36:4 forms) were presumed to be qualitative markers of S. cirsii mycelium.

Identification of lipidomic profiles associated with drug-resistant prostate cancer cells

BackgroundThe association of circulating lipids with clinical outcomes of drug-resistant castration-resistant prostate cancer (DR-CRPC) is not fully understood. While it is known that increases in select lipids correlate to decreased survival, neither the mechanisms mediating these alterations nor the correlation of resistance to drug treatments is well characterized.MethodsThis gap-in-knowledge was addressed using in vitro models of non-cancerous, hormone-sensitive, CRPC and drug-resistant cell lines combined with quantitative LC-ESI-Orbitrap-MS (LC-ESI-MS/MS) lipidomic analysis and subsequent analysis such as Metaboanalyst and Lipid Pathway Enrichment Analysis (LIPEA).ResultsSeveral lipid regulatory pathways were identified that are associated with Docetaxel resistance in prostate cancer (PCa). These included those controlling glycerophospholipid metabolism, sphingolipid signaling and ferroptosis. In total, 7460 features were identified as being dysregulated between the cell lines studied, and 21 lipid species were significantly altered in drug-resistant cell lines as compared to nonresistant cell lines. Docetaxel resistance cells (PC3-Rx and DU145-DR) had higher levels of phosphatidylcholine (PC), oxidized lipid species, phosphatidylethanolamine (PE), and sphingomyelin (SM) as compared to parent control cells (PC-3 and DU-145). Alterations were also identified in the levels of phosphatidic acid (PA) and diacylglyceride (DAG), whose levels are regulated by Lipin (LPIN), a phosphatidic acid phosphatase that converts PA to DAG. Data derived from cBioPortal demonstrated a population of PCa patients expressing mutations aligning with amplification of LPIN1, LPIN2 and LPIN3 genes. Lipin amplification in these genes correlated to decreased survival in these patients. Lipin-1 mRNA expression also showed a similar trend in PCa patient data. Lipin-1, but not Lipin-2 or − 3, was detected in several prostate cancer cells, and was increased in 22RV1 and PC-3 cell lines. The increased expression of Lipin-1 in these cells correlated with the level of PA.ConclusionThese data identify lipids whose levels may correlate to Docetaxel sensitivity and progression of PCa. The data also suggest a correlation between the expression of Lipin-1 in cells and patients with regards to prostate cancer cell aggressiveness and patient survivability. Ultimately, these data may be useful for identifying markers of lethal and/or metastatic prostate cancer.

Abstract 3740: Role of phosphatidylcholine in β-catenin-driven hepatocellular carcinoma

Abstract Introduction: This study aimed to clarify the role of phosphatidylcholine (PC) and choline metabolites in β-catenin-driven hepatocellular carcinoma (HCC) using human HCC cell lines and transgenic zebrafish expressing hepatocyte-specific activated β-catenin. Background: β-catenin is widely believed to be a major oncogene in HCC. PC is one of the major constituents of biological membranes and is synthesized via the phosphatidylethanolamine N-methyltransferase (PEMT) and cytidine diphosphate (CDP)-choline pathways in the liver. Several studies have reported that changes in gene expression and enzyme activity lead to altered PC synthesis in cancer, which contributes to malignant growth. However, the role of altered PC synthesis in HCC and the contribution of activated β-catenin to changes in PC metabolism have not been fully explored. Methods and Results: Transgenic zebrafish expressing hepatocyte-specific activated β-catenin develop HCC as adults and show significant liver enlargement during larval development due to increased cell proliferation. We measured PC levels in transgenic zebrafish HCC and non-transgenic control livers using liquid chromatography-mass spectrometry (LC-MS). PC levels in transgenic zebrafish HCC were significantly higher than in controls. Using a colorimetric assay kit, we found that PC levels were significantly higher in human HCC cell lines (SNU398, C3A and PLC/PRF/5) than in immortalized human hepatocytes (THLE2). To clarify the role of PC and choline metabolites in β-catenin-driven liver overgrowth, we treated larval zebrafish with bezafibrate (PEMT inhibitor) or meclofenoxate (CPT/CEPT inhibitor). We found that both of these inhibitors of PC lipid synthesis reduced larval liver size and decreased the number of EdU-labeled proliferative cells in transgenic zebrafish. Histologically, nonalcoholic steatohepatitis (NASH)-like changes, such as steatosis, ballooning, inflammation, and hepatocellular necrosis, were detected in the livers of transgenic larvae treated with bezafibrate or meclofenoxate. To characterize the role of PC in human HCC cell lines, we treated SNU398, C3A and PLC/PRF/5 cells with bezafibrate or meclofenoxate and measured PC levels by colorimetric assay and viability by CellTiter-Glo Assay. We found that both drugs decreased PC levels and viability in these HCC cell lines. Furthermore, SNU398 cells overexpressing activated β-catenin using a Tet-on system demonstrated higher PC levels and greater viability than SNU398 control cells. Conclusion: Our results suggest that increased PC synthesis is associated with cell proliferation, zebrafish larval liver overgrowth, and hepatocarcinogenesis. These results also suggest that activated β-catenin may regulate choline metabolites and contribute to an increase in PC production. Citation Format: Junko Kuramoto, Richard Smith, Sharanya M. Kalasekar, Alexis Fulbright, Gregory S. Ducker, Kimberley J. Evason. Role of phosphatidylcholine in β-catenin-driven hepatocellular carcinoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3740.

Methyl jasmonate alleviates chilling injury by regulating membrane lipid composition in green bell pepper

The effects of methyl jasmonate (MeJA) treatment on membrane lipid metabolism of green bell pepper during cold storage was studied. The results showed that the chilling injury (CI) index, electrolyte leakage, malondialdehyde (MDA) content, phospholipase D (PLD) activity and gene expression of green bell pepper treated with MeJA were lower than those of the control fruit. MeJA treatment was able to maintain a higher level of ascorbic acid (VC) content, higher levels of phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylserine (PS) and lower levels of digalactosyldiacylglycerol (DGDG), phosphatidic acid (PA), digalactosyldiacylglycerol/monogalactosyldiacylglycerol (DGDG/MGDG) and PC/PE compared to control fruit. In addition, MeJA treatment can also increase the proline content of green bell pepper fruit. Therefore, the reason that MeJA can improve the cold resistance of green bell pepper fruit may be attributed by the decreased expression and activity of PLD gene. The degradation of membrane lipid was delayed, and the content of proline increased, thereby maintaining cell membrane stability.

The effect of citrulline and arginine supplementation on lactic acidemia in MELAS syndrome

Myocardial mitochondria dysfunction seems to represent an important pathogenic factor underlying cardiomyopathy, a common complication of type 1 diabetes mellitus (T1DM). Despite significant progress in the understanding of the molecular mechanisms of mitochondrial function in the heart, the interplay between phospholipids and membrane proteins of this organelle is still poorly comprehended. Using a well-characterized animal model of T1DM obtained by the administration of streptozotocin, phospholipid profiling of isolated mitochondria was performed using MS-based approaches, which was analyzed together with oxidative phosphorylation (OXPHOS) complexes activities and their susceptibility to oxidation, and the expression of cytochrome c, the uncoupling protein UCP-3 and the mitochondrial transcription factor Tfam. Although in higher amounts, mitochondria from T1DM heart presented lower OXPHOS activity and lower transcription ability. This profile was related to phospholipid (PL) remodeling characterized by higher phosphatidylcholine levels, lower phosphatidylglycerol, phosphatidylinositol and sphingomyelin content, higher amounts of long fatty acyl side chains and increased lipid peroxidation, particularly of cardiolipin (CL). CL peroxidation was paralleled by lower cytochrome c content. Though in higher levels, UCP-3 does not seem to protect heart mitochondrial PL and membrane proteins from the oxidative damage induced by four weeks of hyperglycemia. Taken together, our data suggest that PL remodeling of heart mitochondria is an early event in T1DM pathogenesis and is related with OXPHOS dysfunction.

Lipidomic characterization of streptozotocin-induced heart mitochondrial dysfunction

Myocardial mitochondria dysfunction seems to represent an important pathogenic factor underlying cardiomyopathy, a common complication of type 1 diabetes mellitus (T1DM). Despite significant progress in the understanding of the molecular mechanisms of mitochondrial function in the heart, the interplay between phospholipids and membrane proteins of this organelle is still poorly comprehended. Using a well-characterized animal model of T1DM obtained by the administration of streptozotocin, phospholipid profiling of isolated mitochondria was performed using MS-based approaches, which was analyzed together with oxidative phosphorylation (OXPHOS) complexes activities and their susceptibility to oxidation, and the expression of cytochrome c, the uncoupling protein UCP-3 and the mitochondrial transcription factor Tfam. Although in higher amounts, mitochondria from T1DM heart presented lower OXPHOS activity and lower transcription ability. This profile was related to phospholipid (PL) remodeling characterized by higher phosphatidylcholine levels, lower phosphatidylglycerol, phosphatidylinositol and sphingomyelin content, higher amounts of long fatty acyl side chains and increased lipid peroxidation, particularly of cardiolipin (CL). CL peroxidation was paralleled by lower cytochrome c content. Though in higher levels, UCP-3 does not seem to protect heart mitochondrial PL and membrane proteins from the oxidative damage induced by four weeks of hyperglycemia. Taken together, our data suggest that PL remodeling of heart mitochondria is an early event in T1DM pathogenesis and is related with OXPHOS dysfunction.

Age-related changes in mitochondrial membrane composition of rainbow trout (Oncorhynchus mykiss) heart and brain

Membrane composition, particularly of mitochondria, could be a critical factor by determining the propagation of reactions involved in mitochondrial function during periods of high oxidative stress such as rapid growth and aging. Considering that phospholipids not only contribute to the structural and physical properties of biological membranes, but also participate actively in cell signaling and apoptosis, changes affecting either class or fatty acid compositions could affect phospholipid properties and, thus, alter mitochondrial function and cell viability. In the present study, heart and brain mitochondrial membrane phospholipid compositions were analyzed in rainbow trout during the four first years of life, a period characterized by rapid growth and a sustained high metabolic rate. Specifically, farmed fish of three ages (1-, 2- and 4-years) were studied, and phospholipid class compositions of heart and brain mitochondria, and fatty acid compositions of individual phospholipid classes were determined. Rainbow trout heart and brain mitochondria showed different phospholipid compositions (class and fatty acid), likely related to tissue-specific functions. Furthermore, changes in phospholipid class and fatty acid compositions with age were also tissue-dependent. Heart mitochondria had lower proportions of cardiolipin (CL), phosphatidylserine (PS) and phosphatidylinositol, and higher levels of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) with age. Heart mitochondrial membranes became more unsaturated with age, with a significative increase of peroxidation index in CL, PS and sphingomyelin (SM). Therefore, heart mitochondria became more susceptible to oxidative damage with age. In contrast, brain mitochondrial PC and PS content decreased in 4-year-old animals while there was an increase in the proportion of SM. The three main phospholipid classes in brain (PC, PE and PS) showed decreased n-3 polyunsaturated fatty acids, docosahexaenoic acid and peroxidation index, which indicate a different response of brain mitochondrial lipids to rapid growth and maturation.

Effects of dietary levels and ratio of phosphatidylcholine and phosphatidylinositol on the growth, survival and deformity levels of Atlantic cod larvae and early juveniles

Effects of two weaning diets that differed in phospholipid (PL) classes on growth, survival and deformities of cod larvae and early juveniles were evaluated. Cod larvae were fed rotifers until 21 days post hatch (dph) and then weaning onto dry diet started. One group of larvae were fed a control diet with low levels of phosphatidylcholine (PC), PE and phosphatidylinositol (PI) and the other group of larvae were fed with an experimental diet containing higher levels of PC, PE and PI. Larvae fed with the control diet were significantly smaller than larvae fed with the experimental diet at the end of the experiment. Swim bladder abnormalities were significantly higher in larvae fed with control diet at 35 dph than the larvae fed with experimental diet; however, no significant difference was evident at 42 dph. Vertebral deformities were significantly higher in larvae fed with control diet and scoliosis was significantly different between the treatments. Survival was also significantly higher in the experimental group. Our results indicate that dietary levels of PL, PC and PI may affect the cod larval growth, survival and deformities. More detail studies are needed to find out the optimal levels of these important PL classes in larval cod diets.

Transient in utero disruption of Cystic Fibrosis Transmembrane Conductance Regulator causes phenotypic changes in Alveolar Type II cells in adult rats

BackgroundMechanicosensory mechanisms regulate cell differentiation during lung organogenesis. We have previously demonstrated that cystic fibrosis transmembrane conductance regulator (CFTR) was integral to stretch-induced growth and development and that transient expression of antisense-CFTR (ASCFTR) had negative effects on lung structure and function. In this study, we examined adult alveolar type II (ATII) cell phenotype after transient knock down of CFTR by adenovirus-directed in utero expression of ASCFTR in the fetal lung.ResultsIn comparison to (reporter gene-treated) Controls, ASCFTR-treated adult rat lungs showed elevated phosphatidylcholine (PC) levels in the large but not in the small aggregates of alveolar surfactant. The lung mRNA levels for SP-A and SP-B were lower in the ASCFTR rats. The basal PC secretion in ATII cells was similar in the two groups. However, compared to Control ATII cells, the cells in ASCFTR group showed higher PC secretion with ATP or phorbol myristate acetate. The cell PC pool was also larger in the ASCFTR group. Thus, the increased surfactant secretion in ATII cells could cause higher PC levels in large aggregates of surfactant. In freshly isolated ATII cells, the expression of surfactant proteins was unchanged, suggesting that the lungs of ASCFTR rats contained fewer ATII cells. Gene array analysis of RNA of freshly isolated ATII cells from these lungs showed altered expression of several genes including elevated expression of two calcium-related genes, Ca2+-ATPase and calcium-calmodulin kinase kinase1 (CaMkk1), which was confirmed by real-time PCR. Western blot analysis showed increased expression of calmodulin kinase I, which is activated following phosphorylation by CaMkk1. Although increased expression of calcium regulating genes would argue in favor of Ca2+-dependent mechanisms increasing surfactant secretion, we cannot exclude contribution of alternate mechanisms because of other phenotypic changes in ATII cells of the ASCFTR group.ConclusionDevelopmental changes due to transient disruption of CFTR in fetal lung reflect in altered ATII cell phenotype in the adult life.

Nuclear lipid microdomains regulate cell function

The lipids present in the nuclei play different roles in relation to their localization. They are composed by high levels of phosphatidylcholine and sphingomyelin strongly linked with cholesterol. The nuclear lipid composition shows many modifications during cell life due to the presence and activity of some specific enzymes such as sphingomyelinase, sphingomyelin-synthase, reverse sphingomyelin-syntase and phosphatidylcholine-specific phospholipase C. These lipids are associated with a small amount of DNA, with the new-synthesized double-strand RNA, and with proteins to form an intranuclear complex that it is not possible to extract with the techniques used for nuclear membrane and chromatin purification. The intranuclear complex represents a section of inner nuclear membrane that binds to the active chromatin. In a recent paper, we have demonstrated that this complex actually constitutes the lipid microdomains present in the inner nuclear membrane and represents a platform for the transcription process. The possible model of action is reported in this addendum article.

Lipid Microdomains in Cell Nucleus

It is known that nuclear lipids play a role in proliferation, differentiation, and apoptotic process. Cellular nuclei contain high levels of phosphatidylcholine and sphingomyelin, which are partially linked with cholesterol and proteins to form lipid-protein complexes. These lipids are also associated with transcription factors and newly synthesized RNA but, up to date, their organization is still unknown. The aim of the present work was to study if these specific lipid-protein interactions could be nuclear membrane microdomains and to evaluate their possible role. The results obtained demonstrate for the first time the existence of nuclear microdomains characterized by a specific lipid composition similar to that of intranuclear lipid-protein complexes previously described. Nuclear microdomain lipid composition changes during cell proliferation when the content of newly synthesized RNA increases. Because previous data show a correlation between nuclear lipids and transcription process, the role of nuclear microdomains in cellular functions is discussed.

Lipidomic analysis of Toxoplasma gondii reveals unusual polar lipids.

Analysis of the polar lipids of Toxoplasma gondii by electrospray ionization tandem mass spectrometry provides a detailed picture of the lipid molecular species of this parasitic protozoan. Most notably, T. gondii contains a relatively high level, estimated to about 2% of the total polar lipid, of ceramide phosphoethanolamine. The ceramide phosphoethanolamine has a fatty amide profile with only 16- and 18-carbon species. Compared with the host fibroblasts in which it was grown, T. gondii also has higher levels of phosphatidylcholine but lower levels of sphingomyelin and phosphatidylserine. Analysis at the molecular species level indicated that T. gondii has greater amounts of shorter-chain fatty acid in its polar lipid molecular species than the host fibroblasts. Shorter-chain fatty acids with a combined total of 30 or fewer acyl carbons make up 21% of Toxoplasma's, but only 3% of the host's, diacyl phosphatidylcholine. Furthermore, diacyl phosphatidylcholine with two saturated acyl chains with 12, 14, or 16 carbons make up over 11% of parasite phosphatidylcholine but less than 3% of the host phosphatidylcholine molecular species. The distinctive T. gondii tachyzoite lipid profile may be particularly suited to the function of parasitic membranes and the interaction of the parasite with the host cell and the host's immune system. Combined with T. gondii genomic data, these lipidomic data will assist in elucidation of metabolic pathways for lipid biosynthesis in this important human pathogen.

Increased lung surfactant phosphatidylcholine in patients affected by lysosomal storage diseases

Sandhoff disease, Gaucher disease type I and sialidosis type I are lysosomal storage disorders caused, respectively, by deficiency of activity of beta-hexosaminidase (storage of GM(2) and GA(2) ganglioside), glucosylceramidase (storage of glucosylceramide) and alpha-neuraminidase (storage of glucopeptides and/or oligosaccharides). Progressive clinical systemic and neurological dysfunctions are observed. In these pathologies, respiratory infections often lead to death. Elevation of the lung surfactant phosphatidylcholine (PC) has previously been reported in the Hexb mouse, a model of Sandhoff disease. We evaluated phospholipids in the lung surfactant of patients affected by the described lysosomal diseases, observing a statistically significant increase of total lipid phosphate in the patients as compared with controls. Moreover, higher levels of PC in patients affected by sialidosis (3.6-fold) and Gaucher (4-fold) disease, and of PC (4.15-fold) and phosphatidylethanolamine (2.3-fold) in a patient affected by Sandhoff disease were noted. The latter confirms the previous results in the Hexb mouse. We suggest that changes in phospholipid metabolism can be common in different lysosomal storage disorders and can increase the susceptibility to respiratory infections, usually present in these disorders.

Qualitative needs of lipids by mullet, Mugil cephalus, fry during freshwater acclimation

The mass evolution of phospholipids and triacylglycerols of mullet fry was studied using a decreasing salinity (0.5‰) at constant temperature. After 4 weeks of acclimation (0.5‰), high concentrations of phospholipids (9.75 mg/g wet weight) and triacylglycerols (49.77 μmoles/g w/w) were observed in fry acclimated in seawater (35‰) compared to fry in freshwater (0.5‰) which had levels of 6.56 mg/g w/w and 7.32 μmol/g w/w, respectively. Significantly, high levels of phosphatidylcholine (PC) were observed in fry acclimated to freshwater (960.48 μg/g w/w) compared to those in seawater (591.97 μg/g w/w). Radioactivity distribution, after injection of labelled acetate at 14C, was significantly higher in fry acclimated to seawater in the triacylglycerol. However, high levels of radioactivity were incorporated in PC in fry acclimated to freshwater. High levels of PC in fry acclimated to freshwater could serve as precursor synthesis of triacylglycerols. The enrichment of food for mullet fry with lecithin (PC) is necessary during acclimation before their introduction into freshwater (0.5‰) to reduce mortality.

Pulmonary Surfactant from Healthy Belgian White and Blue and Holstein Friesian Calves: Biochemical and Biophysical Comparison

The biochemical composition and biophysical behaviour of pulmonary surfactant samples isolated from healthy Belgian White and Blue (BWB) and Holstein Friesian (HF) calves have been investigated and compared. Interesting differences in composition have been demonstrated. In particular, a higher level of total hydrophobic surfactant-associated proteins (SP) (due to higher levels of SP-B and SP-C) is reported in HF calves compared to BWB calves. Higher levels of phosphatidylcholine (PC) and especially the disaturated form of PC were also found in HF as compared to BWB calves. No immediate effect on the surface tension properties evaluated by the pulsating bubble surfactometer was found between the surfactant samples of the two breeds under physiological conditions. However, since a high content of disaturated PC and the presence of the SP-B and SP-C are thought to be essential for the surface activity, we propose that the reported modifications could contribute to the apparently lower resistance of the BWB calves to respiratory troubles in comparison with HF calves.

Pulmonary-type surfactants in the lungs of terrestrial and aquatic amphibians

We examined the composition and function of pulmonary surfactants in amphibians inhabiting aquatic and terrestrial habitats with particular regard to the influences of (1) variations in body temperature, (2) external hydrostatic pressure and (3) breathing pattern. Two fully aquatic salamanders, and the completely terrestrial cane toad Bufo marinus (all maintained at 21–23 °C) were selected. Whereas one of the salamanders ( Siren intermedia) possessed gills and lungs, Amphiuma tridactylum only possessed lungs. We determined the amounts of cholesterol (Chol), disaturated phospholipids (DSP) and total phospholipid (PL) in lavage of all three species, and also determined the types of phospholipids of B. marinus and A. tridactylum. DSP lowers surface tension at the air-water interface in the lung, while Chol and unsaturated phospholipids assist spreading and maintain the DSP in its disordered, liquid-crystalline state at high lung volumes. All three species had significant amounts of pulmonary-type surfactant. The two aquatic salamanders had identical ratios of both Chol/PL and DSP/PL both of which in turn were nearly twice those of B. marinus. All three species had similar Chol/DSP ratios. Aquatic salamanders sustain high external hydrostatic pressure exerted by the aquatic environment and tend to collapse their lungs during expiration. We hypothesize that these salamanders might require a DSP-rich surfactant to prevent the epithelial surfaces from adhering and large amounts of Chol to keep the DSP fluid. The terrestrial B. marinus has less DSP, suggesting a surfactant which is fluid over a large range of temperatures. Possibly, cane toads do not require a DSP rich surfactant as they either collapse their lungs on deflation, nor experience external hydrostatic pressure promoting lung collapse. The PL profile of B. marinus lavage was similar to that of other frogs and mammals, containing phosphatidylcholine (PC) as the predominant phospholipid together with substantial amounts of phosphatidyglycerol (PG). On the other hand, although A. tridactylum exhibited high levels of PC, it contained phosphatidylinositol (PI) in place of PG, a pattern typical of reptiles and birds.

Oxidant sensitivity of the zinc-thiolate moiety of yeast alcohol dehydrogenase

The biochemical composition and biophysical behaviour of pulmonary surfactant samples isolated from healthy Belgian White and Blue (BWB) and Holstein Friesian (HF) calves have been investigated and compared. Interesting differences in composition have been demonstrated. In particular, a higher level of total hydrophobic surfactant-associated proteins (SP) (due to higher levels of SP-B and SP-C) is reported in HF calves compared to BWB calves. Higher levels of phosphatidylcholine (PC) and especially the disaturated form of PC were also found in HF as compared to BWB calves. No immediate effect on the surface tension properties evaluated by the pulsating bubble surfactometer was found between the surfactant samples of the two breeds under physiological conditions. However, since a high content of disaturated PC and the presence of the SP-B and SP-C are thought to be essential for the surface activity, we propose that the reported modifications could contribute to the apparently lower resistance of the BWB calves to respiratory troubles in comparison with HF calves.