scholarly journals Phosphoinositide Profile of the Mouse Retina

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1417
Author(s):  
Stella Finkelstein ◽  
Sidney M. Gospe ◽  
Kai Schuhmann ◽  
Andrej Shevchenko ◽  
Vadim Y. Arshavsky ◽  
...  
Keyword(s):  
High Resolution Mass Spectrometry ◽  
Biological Significance ◽  
Distribution Patterns ◽  
Fatty Acyl ◽  
Multiple Roles ◽  
Mouse Retina ◽  
Phosphoinositide Metabolism ◽  
Synaptic Region ◽  
Acyl Chains ◽  
Photoreceptor Neurons

Phosphoinositides are known to play multiple roles in eukaryotic cells. Although dysregulation of phosphoinositide metabolism in the retina has been reported to cause visual dysfunction in animal models and human patients, our understanding of the phosphoinositide composition of the retina is limited. Here, we report a characterization of the phosphoinositide profile of the mouse retina and an analysis of the subcellular localization of major phosphorylated phosphoinositide forms in light-sensitive photoreceptor neurons. Using chromatography of deacylated phosphatidylinositol headgroups, we established PI(4,5)P2 and PI(4)P as two major phosphorylated phosphoinositides in the retina. Using high-resolution mass spectrometry, we revealed 18:0/20:4 and 16:0/20:4 as major fatty-acyl chains of retinal phosphoinositides. Finally, analysis of fluorescent phosphoinositide sensors in rod photoreceptors demonstrated distinct subcellular distribution patterns of major phosphoinositides. The PI(4,5)P2 reporter was enriched in the inner segments and synapses, but was barely detected in the light-sensitive outer segments. The PI(4)P reporter was mostly found in the outer and inner segments and the areas around nuclei, but to a lesser degree in the synaptic region. These findings provide support for future mechanistic studies defining the biological significance of major mono- (PI(4)P) and bisphosphate (PI(4,5)P2) phosphatidylinositols in photoreceptor biology and retinal health.

Microstructural morphology of sphingolipid dispersions as investigated by freeze-fracture EM

1995 ◽  
Vol 53 ◽  
pp. 944-945
Author(s):  
Vitthal S. Kulkarni ◽  
Wayne H. Anderson ◽  
Rhoderick E. Brown
Keyword(s):  
Acyl Chain ◽  
Biological Significance ◽  
Freeze Fracture ◽  
Fatty Acyl ◽  
Fatty Acyl Moiety ◽  
Aqueous Dispersions ◽  
Head Groups ◽  
Lipid Species ◽  
Microstructural Morphology ◽  
Layer Chromatography

The biological significance of the sphingomyelins (SM) and monoglycosylated sphingolipids like galactosylceramides (GalCer) are well documented Our recent investigation showed tubular bilayers in the aqueous dispersions of N-nervonoyl GalCer [N-(24:lΔ15,cls) GalCer] (a major fatty acyl moiety of natural GalCer). To determine the influence of lipid head groups on the resulting mesophasic morphology, we investigated microstructural self-assemblies of N-nervonoyl-SM [N-(24:1 Δ15,cls) SM; the second most abundant sphingomyelin in mammalian cell membranes], 1- palmitoyl-2-nervonoyl phosphatidylcholine [PNPC] (the lipid species with the same acyl chain configuration as in N-(24: 1) GalCer) and also compared it with egg-SM by freeze-fracture EM.Procedures for synthesizing and purifying N-(24:1) GalCer, N-(24:1) SM, and PNPC have been reported . Egg-SM was purchased from Avanti Polar Lipids, Alabaster AL. All lipids were >99% pure as checked by thin layer chromatography. Lipid dispersions were prepared by hydrating dry lipid with phosphate buffer (pH 6.6) at 80-90°C (3-5 min), vigorously vortexing (1 min) and repeating this procedure for three times prior to three freeze-thaw cycles.

scholarly journals Diethylstilbestrol Modifies the Structure of Model Membranes and Is Localized Close to the First Carbons of the Fatty Acyl Chains

Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 220
Author(s):  
Alessio Ausili ◽  
Inés Rodríguez-González ◽  
Alejandro Torrecillas ◽  
José A. Teruel ◽  
Juan C. Gómez-Fernández
Keyword(s):  
Membrane Surface ◽  
Water Layer ◽  
Fatty Acyl ◽  
31P Nmr Spectroscopy ◽  
Relaxation Rates ◽  
X Ray Diffraction ◽  
Scanning Calorimetry ◽  
X Ray ◽  
Acyl Chains ◽  
Dynamics Simulations

The synthetic estrogen diethylstilbestrol (DES) is used to treat metastatic carcinomas and prostate cancer. We studied its interaction with membranes and its localization to understand its mechanism of action and side-effects. We used differential scanning calorimetry (DSC) showing that DES fluidized the membrane and has poor solubility in DMPC (1,2-dimyristoyl-sn-glycero-3-phosphocholine) in the fluid state. Using small-angle X-ray diffraction (SAXD), it was observed that DES increased the thickness of the water layer between phospholipid membranes, indicating effects on the membrane surface. DSC, X-ray diffraction, and 31P-NMR spectroscopy were used to study the effect of DES on the Lα-to-HII phase transition, and it was observed that negative curvature of the membrane is promoted by DES, and this effect may be significant to understand its action on membrane enzymes. Using the 1H-NOESY-NMR-MAS technique, cross-relaxation rates for different protons of DES with POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine) protons were calculated, suggesting that the most likely location of DES in the membrane is with the main axis parallel to the surface and close to the first carbons of the fatty acyl chains of POPC. Molecular dynamics simulations were in close agreements with the experimental results regarding the location of DES in phospholipids bilayers.

How do mechanosensitive channels sense membrane tension?

2016 ◽  
Vol 44 (4) ◽  
pp. 1019-1025 ◽  
Author(s):  
Tim Rasmussen
Keyword(s):  
Membrane Lipids ◽  
Osmotic Shock ◽  
Md Simulations ◽  
Fatty Acyl ◽  
Membrane Bilayer ◽  
Cross Sectional ◽  
Conducting Path ◽  
Lipid Chain ◽  
Acyl Chains

Mechanosensitive (MS) channels provide protection against hypo-osmotic shock in bacteria whereas eukaryotic MS channels fulfil a multitude of important functions beside osmoregulation. Interactions with the membrane lipids are responsible for the sensing of mechanical force for most known MS channels. It emerged recently that not only prokaryotic, but also eukaryotic, MS channels are able to directly sense the tension in the membrane bilayer without any additional cofactor. If the membrane is solely viewed as a continuous medium with specific anisotropic physical properties, the sensitivity towards tension changes can be explained as result of the hydrophobic coupling between membrane and transmembrane (TM) regions of the channel. The increased cross-sectional area of the MS channel in the active conformation and elastic deformations of the membrane close to the channel have been described as important factors. However, recent studies suggest that molecular interactions of lipids with the channels could play an important role in mechanosensation. Pockets in between TM helices were identified in the MS channel of small conductance (MscS) and YnaI that are filled with lipids. Less lipids are present in the open state of MscS than the closed according to MD simulations. Thus it was suggested that exclusion of lipid fatty acyl chains from these pockets, as a consequence of increased tension, would trigger gating. Similarly, in the eukaryotic MS channel TRAAK it was found that a lipid chain blocks the conducting path in the closed state. The role of these specific lipid interactions in mechanosensation are highlighted in this review.

scholarly journals Acyltransferase-mediated selection of the length of the fatty acyl chain and of the acylation site governs activation of bacterial RTX toxins

2020 ◽  
Vol 295 (28) ◽  
pp. 9268-9280 ◽  
Author(s):  
Adriana Osickova ◽  
Humaira Khaliq ◽  
Jiri Masin ◽  
David Jurnecka ◽  
Anna Sukova ◽  
...  
Keyword(s):  
Acyl Chain ◽  
Fatty Acyl ◽  
Biologically Active ◽  
Fatty Acyl Chain ◽  
Acyl Carrier Proteins ◽  
E Coli ◽  
Rtx Toxins ◽  
Wide Range ◽  
Lysine Residues ◽  
Acyl Chains

In a wide range of organisms, from bacteria to humans, numerous proteins have to be posttranslationally acylated to become biologically active. Bacterial repeats in toxin (RTX) cytolysins form a prominent group of proteins that are synthesized as inactive protoxins and undergo posttranslational acylation on ε-amino groups of two internal conserved lysine residues by co-expressed toxin-activating acyltransferases. Here, we investigated how the chemical nature, position, and number of bound acyl chains govern the activities of Bordetella pertussis adenylate cyclase toxin (CyaA), Escherichia coli α-hemolysin (HlyA), and Kingella kingae cytotoxin (RtxA). We found that the three protoxins are acylated in the same E. coli cell background by each of the CyaC, HlyC, and RtxC acyltransferases. We also noted that the acyltransferase selects from the bacterial pool of acyl–acyl carrier proteins (ACPs) an acyl chain of a specific length for covalent linkage to the protoxin. The acyltransferase also selects whether both or only one of two conserved lysine residues of the protoxin will be posttranslationally acylated. Functional assays revealed that RtxA has to be modified by 14-carbon fatty acyl chains to be biologically active, that HlyA remains active also when modified by 16-carbon acyl chains, and that CyaA is activated exclusively by 16-carbon acyl chains. These results suggest that the RTX toxin molecules are structurally adapted to the length of the acyl chains used for modification of their acylated lysine residue in the second, more conserved acylation site.

scholarly journals Increased fatty acyl saturation of phosphatidylinositol phosphates in prostate cancer progression

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Atsushi Koizumi ◽  
Shintaro Narita ◽  
Hiroki Nakanishi ◽  
Masaki Ishikawa ◽  
Satoshi Eguchi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Progression ◽  
Fatty Acyl ◽  
Human Prostate ◽  
Pathological Stage ◽  
Double Bonds ◽  
Prostate Hyperplasia ◽  
Cellular Processes ◽  
Acyl Chains ◽  
Phosphatidylinositol Phosphates

Abstract Phosphoinositides (PIPs) participate in many cellular processes, including cancer progression; however, the metabolic features of PIPs associated with prostate cancer (PCa) are unknown. We investigated PIPs profiles in PTEN-deficient prostate cancer cell lines, human prostate tissues obtained from patients with PCa and benign prostate hyperplasia (BPH) specimens using mass spectrometry. In immortalized normal human prostate PNT1B cells, PTEN deficiency increased phosphatidylinositol tris-phosphate (PIP3) and decreased phosphatidylinositol mono- and bis-phosphate (PIP1 and PIP2), consistent with PTEN’s functional role as a PI(3,4,5)P3 3-phosphatase. In human prostate tissues, levels of total (sum of all acyl variants) phosphatidylinositol (PI) and PIP1 in PCa were significantly higher than in BPH, whereas PIP2 and PIP3 contents were significantly lower than in BPH. PCa patients had significantly higher proportion of PI, PIP1, and PIP2 with 0–2 double bonds in acyl chains than BPH patients. In subgroup analyses based on PCa aggressiveness, mean total levels of PI with 0–2 double bonds in acyl chains were significantly higher in patients with pathological stage T3 than in those with pathological stage T2. These data indicate that alteration of PIPs level and the saturation of acyl chains may be associated with the development and aggressiveness of prostate cancer, although it is unknown whether this alteration is causative.

scholarly journals Fluorescence distribution pattern allows to distinguish two species of Eugymnanthea (Leptomedusae: Eirenidae)

2008 ◽  
Vol 88 (8) ◽  
pp. 1743-1746 ◽  
Author(s):  
Shin Kubota ◽  
Patrizia Pagliara ◽  
Cinzia Gravili
Keyword(s):  
Distribution Pattern ◽  
Blue Light ◽  
Biological Significance ◽  
Distribution Patterns ◽  
Taxonomic Character ◽  
Green Fluorescence ◽  
Short Life ◽  
Fluorescent Microscope ◽  
Light Excitation ◽  
Auto Fluorescence

The auto-fluorescence patterns of the medusae observed under a fluorescent microscope with blue light excitation allows to distinguish two species of Eugymnanthea, this even when they are still attached to the hydroid as small medusa buds despite the occurrence of a sex-dependant pattern in E. japonica. A total of four distribution patterns of green fluorescence, including non-fluorescence, could be found. Three of them are found in E. japonica, called ‘subumbrellar fluorescence type’ except for non-fluorescence, while another type is found in E. inquilina, called ‘umbrellar margin fluorescence type’. During the short life of the medusa the latter type remained invariable for up to six days in E. inquilina, while the pattern observed for up to seven days in E. japonica changed sometimes, but it always remained distinguishable from the pattern found in E. inquilina. Therefore, the fluorescence pattern is a reliable taxonomic character. Fluorescence was not found in unfertilized eggs, planulae 2–8 days old, parthenogenetically produced larvae, or in the hydroids of the two species. The auto-fluorescent and possible bioluminescent tissues of these Eugymnanthea medusae could have some unknown biological significance.

scholarly journals Effect of the Degree of Substitution on the Hydrophobicity, Crystallinity, and Thermal Properties of Lauroylated Amaranth Starch

Polymers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 2548
Author(s):  
Vicente Espinosa-Solis ◽  
Yunia Verónica García-Tejeda ◽  
Everth Jimena Leal-Castañeda ◽  
Víctor Barrera-Figueroa
Keyword(s):  
Photoelectron Spectroscopy ◽  
Thermal Characterization ◽  
Fatty Acyl ◽  
Degree Of Substitution ◽  
X Ray Diffraction ◽  
Scanning Calorimetry ◽  
X Ray ◽  
Amaranthus Hypochondriacus ◽  
Two Samples ◽  
Acyl Chains

In this paper, we consider amaranth starch extracted from the seeds of Amaranthus hypochondriacus L. An amphiphilic character is conferred to the starch by a chemical modification, which involves an esterification by lauroyl chloride at three modification levels. The degree of substitution (DS) after the modification ranged from 0.06 to 1.16. X-ray photoelectron spectroscopy analysis confirmed the presence of fatty acyl chains on the surface of the esterified starches. The hydrophobicity of starches was confirmed by their adsorption isotherms, which showed a decrease in the moisture adsorption of lauroylated as DS increased. X-ray diffraction analysis revealed a higher crystallinity, which was observed in the two samples subjected to the highest levels of modification. A higher crystallinity is related to a higher gelatinization enthalpy. These results are in agreement with the thermal characterization obtained by differential scanning calorimetry (DSC). An inhibition of the retrogradation properties of lauroylated amaranth starches was also observed.

scholarly journals Sexual dimorphism in gastric cancer: tumor-associated neutrophils predict patient outcome only for women

2019 ◽  
Vol 146 (1) ◽  
pp. 53-66 ◽  
Author(s):  
Franziska Clausen ◽  
Hans-Michael Behrens ◽  
Sandra Krüger ◽  
Christoph Röcken
Keyword(s):  
Gastric Cancer ◽  
Patient Outcome ◽  
Sexual Dimorphism ◽  
Biological Significance ◽  
Tumor Grade ◽  
Distribution Patterns ◽  
Patient Characteristics ◽  
Invasion Front ◽  
Tumor Center ◽  
Tumor Associated Neutrophils

Abstract Purpose Tumor-associated neutrophils (TANs) are part of the tumor immune microenvironment (TIME) and may contribute to gastric cancer (GC) biology. We hypothesized that TAN are enriched in the TIME, show sex-specific differences, and correlate with patient outcome. Methods We analyzed the distribution and putative tumor biological significance of TANs in a well-characterized, therapy-naïve, European GC cohort using immunohistochemical staining of myeloperoxidase (MPO), and digital image analysis using Definiens Tissue Studio®. Results Different tumor compartments were examined, and TAN densities were correlated with various clinicopathological patient characteristics. TAN density showed a large interindividual variability ranging from 0 to 6711.0 TANs/mm2. Intratumoral distribution patterns were inhomogeneous (tumor surface vs. tumor center vs. invasion front) and correlated significantly with Laurén phenotype, tumor grade, and microsatellite status in the tumor center and invasion front. In the multivariate analysis, TAN density in the invasion front was an independent predictor of tumor-specific survival only for women (HR = 2.77, p   < 0.001). In men, no correlation was found between TAN density and survival. Conclusion With regard to TANs, our study independently validates sexual dimorphism in GC biology.

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