Browsing by Subject "Phosphatidylcholines"

Now showing 1 - 7 of 7
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    Effects of Lipid Interactions on Model Vesicle Engulfment by Alveolar Macrophages
    (Elsevier B.V., 2014-02-04) Justice, Matthew J.; Petrusca, Daniela N.; Rogozea, Adriana L.; Williams, Justin A.; Schweitzer, Kelly S.; Petrache, Irina; Wassall, Stephen R.; Petrache, Horia I.; Department of Physics, School of Science
    The engulfment function of macrophages relies on complex molecular interactions involving both lipids and proteins. In particular, the clearance of apoptotic bodies (efferocytosis) is enabled by externalization on the cell target of phosphatidylserine lipids, which activate receptors on macrophages, suggesting that (local) specific lipid-protein interactions are required at least for the initiation of efferocytosis. However, in addition to apoptotic cells, macrophages can engulf foreign bodies that vary substantially in size from a few nanometers to microns, suggesting that nonspecific interactions over a wide range of length scales could be relevant. Here, we use model lipid membranes (made of phosphatidylcholine, phosphatidylserine, and ceramide) and rat alveolar macrophages to show how lipid bilayer properties probed by small-angle x-ray scattering and solid-state 2H NMR correlate with engulfment rates measured by flow cytometry. We find that engulfment of protein-free model lipid vesicles is promoted by the presence of phosphatidylserine lipids but inhibited by ceramide, in accord with a previous study of apoptotic cells. We conclude that the roles of phosphatidylserine and ceramide in phagocytosis is based, at least in part, on lipid-mediated modification of membrane physical properties, including interactions at large length scales as well as local lipid ordering and possible domain formation.
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    Location of dopamine in lipid bilayers and its relevance to neuromodulator function
    (Elsevier, 2023) Shafieenezhad, Azam; Mitra, Saheli; Wassall, Stephen R.; Tristram-Nagle, Stephanie; Nagle, John F.; Petrache, Horia I.; Physics, School of Science
    Dopamine (DA) is a neurotransmitter that also acts as a neuromodulator, with both functions being essential to brain function. Here, we present the first experimental measurement of DA location in lipid bilayers using x-ray diffuse scattering, solid-state deuterium NMR, and electron paramagnetic resonance. We find that the association of DA with lipid headgroups as seen in electron density profiles leads to an increase of intermembrane repulsion most likely due to electrostatic charging. DA location in the lipid headgroup region also leads to an increase of the cross-sectional area per lipid without affecting the bending rigidity significantly. The order parameters measured by solid-state deuterium NMR decrease in the presence of DA for the acyl chains of PC and PS lipids, consistent with an increase in the area per lipid due to DA. Most importantly, these results support the hypothesis that three-dimensional diffusion of DA to target membranes could be followed by relatively more efficient two-dimensional diffusion to receptors within those membranes.
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    Machine Learning Reveals Lipidome Remodeling Dynamics in a Mouse Model of Ovarian Cancer
    (Cold Spring Harbor Laboratory, 2023-01-04) Bifarin, Olatomiwa O.; Sah, Samyukta; Gaul, David A.; Moore, Samuel G.; Chen, Ruihong; Palaniappan, Murugesan; Kim, Jaeyeon; Matzuk, Martin M.; Fernández, Facundo M.; Biochemistry and Molecular Biology, School of Medicine
    Ovarian cancer (OC) is one of the deadliest cancers affecting the female reproductive system. It may present little or no symptoms at the early stages, and typically unspecific symptoms at later stages. High-grade serous ovarian cancer (HGSC) is the subtype responsible for most ovarian cancer deaths. However, very little is known about the metabolic course of this disease, particularly in its early stages. In this longitudinal study, we examined the temporal course of serum lipidome changes using a robust HGSC mouse model and machine learning data analysis. Early progression of HGSC was marked by increased levels of phosphatidylcholines and phosphatidylethanolamines. In contrast, later stages featured more diverse lipids alterations, including fatty acids and their derivatives, triglycerides, ceramides, hexosylceramides, sphingomyelins, lysophosphatidylcholines, and phosphatidylinositols. These alterations underscored unique perturbations in cell membrane stability, proliferation, and survival during cancer development and progression, offering potential targets for early detection and prognosis of human ovarian cancer.
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    Mutations in the CDP-Choline Pathway for Phospholipid Biosynthesis Bypass the Requirement for an Essential Phospholipid Transfer Protein
    (Cell Press, 1991) Cleves, Ann E.; McGee, Todd P.; Whitters, Eric A.; Champion, Kathleen M.; Aitken, Jacqueline R.; Dowhan, William; Goebl, Mark; Bankaitis, Vytas A.; Biochemistry and Molecular Biology, School of Medicine
    SEC14p is the yeast phosphatidylinositol (PI)/phosphatidylcholine (PC) transfer protein, and it effects an essential stimulation of yeast Golgi secretory function. We now report that the SEC14p localizes to the yeast Golgi and that the SEC14p requirement can be specifically and efficiently bypassed by mutations in any one of at least six genes. One of these suppressor genes was the structural gene for yeast choline kinase (CKI), disruption of which rendered the cell independent of the normally essential SEC14p requirement. The antagonistic action of the CKI gene product on SEC14p function revealed a previously unsuspected influence of biosynthetic activities of the CDP-choline pathway for PC biosynthesis on yeast Golgi function and indicated that SEC14p controls the phospholipid content of yeast Golgi membranes in vivo.
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    Phase Coexistence in Single-Lipid Membranes Induced by Buffering Agents
    (American Chemical Society, 2014-08-26) Johnson, Merrell A.; Seifert, Soenke; Petrache, Horia I.; Kimble-Hill, Ann C.; Department of Biochemistry & Molecular Biology, IU School of Medicine
    Recent literature has shown that buffers affect the interaction between lipid bilayers through a mechanism that involves van der Waals forces, electrostatics, hydration forces and membrane bending rigidity. This letter shows an additional peculiar effect of buffers on the mixed chain 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) lipid bilayers, namely phase coexistence similar to what was reported by Rappolt et al. for alkali chlorides. The data presented suggest that one phase appears to dehydrate below the value in pure water, while the other phase swells as the concentration of buffer is increased. However, since the two phases must be in osmotic equilibrium with one another, this behavior challenges theoretical models of lipid interactions.
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    Regulation of β-cell death by ADP-ribosylhydrolase ARH3 via lipid signaling in insulitis
    (Springer Nature, 2024-02-21) Sarkar, Soumyadeep; Deiter, Cailin; Kyle, Jennifer E.; Guney, Michelle A.; Sarbaugh, Dylan; Yin, Ruichuan; Li, Xiangtang; Cui, Yi; Ramos‑Rodriguez, Mireia; Nicora, Carrie D.; Syed, Farooq; Juan‑Mateu, Jonas; Muralidharan, Charanya; Pasquali, Lorenzo; Evans‑Molina, Carmella; Eizirik, Decio L.; Webb‑Robertson, Bobbie‑Jo M.; Burnum‑Johnson, Kristin; Orr, Galya; Laskin, Julia; Metz, Thomas O.; Mirmira, Raghavendra G.; Sussel, Lori; Ansong, Charles; Nakayasu, Ernesto S.; Pediatrics, School of Medicine
    Background: Lipids are regulators of insulitis and β-cell death in type 1 diabetes development, but the underlying mechanisms are poorly understood. Here, we investigated how the islet lipid composition and downstream signaling regulate β-cell death. Methods: We performed lipidomics using three models of insulitis: human islets and EndoC-βH1 β cells treated with the pro-inflammatory cytokines interlukine-1β and interferon-γ, and islets from pre-diabetic non-obese mice. We also performed mass spectrometry and fluorescence imaging to determine the localization of lipids and enzyme in islets. RNAi, apoptotic assay, and qPCR were performed to determine the role of a specific factor in lipid-mediated cytokine signaling. Results: Across all three models, lipidomic analyses showed a consistent increase of lysophosphatidylcholine species and phosphatidylcholines with polyunsaturated fatty acids and a reduction of triacylglycerol species. Imaging assays showed that phosphatidylcholines with polyunsaturated fatty acids and their hydrolyzing enzyme phospholipase PLA2G6 are enriched in islets. In downstream signaling, omega-3 fatty acids reduce cytokine-induced β-cell death by improving the expression of ADP-ribosylhydrolase ARH3. The mechanism involves omega-3 fatty acid-mediated reduction of the histone methylation polycomb complex PRC2 component Suz12, upregulating the expression of Arh3, which in turn decreases cell apoptosis. Conclusions: Our data provide insights into the change of lipidomics landscape in β cells during insulitis and identify a protective mechanism by omega-3 fatty acids.