scholarly journals Interaction of Local Anesthetics with Biomembranes Consisting of Phospholipids and Cholesterol: Mechanistic and Clinical Implications for Anesthetic and Cardiotoxic Effects

2013 ◽  
Vol 2013 ◽  
pp. 1-18 ◽  
Author(s):  
Hironori Tsuchiya ◽  
Maki Mizogami
Keyword(s):  
Lipid Bilayers ◽  
Local Anesthetics ◽  
Cell Membranes ◽  
Membrane Lipids ◽  
Transmembrane Proteins ◽  
Membrane Lipid ◽  
Direct Inhibition ◽  
Drug Molecules ◽  
Site Of Action ◽  
Lipid Barriers

Despite a long history in medical and dental application, the molecular mechanism and precise site of action are still arguable for local anesthetics. Their effects are considered to be induced by acting on functional proteins, on membrane lipids, or on both. Local anesthetics primarily interact with sodium channels embedded in cell membranes to reduce the excitability of nerve cells and cardiomyocytes or produce a malfunction of the cardiovascular system. However, the membrane protein-interacting theory cannot explain all of the pharmacological and toxicological features of local anesthetics. The administered drug molecules must diffuse through the lipid barriers of nerve sheaths and penetrate into or across the lipid bilayers of cell membranes to reach the acting site on transmembrane proteins. Amphiphilic local anesthetics interact hydrophobically and electrostatically with lipid bilayers and modify their physicochemical property, with the direct inhibition of membrane functions, and with the resultant alteration of the membrane lipid environments surrounding transmembrane proteins and the subsequent protein conformational change, leading to the inhibition of channel functions. We review recent studies on the interaction of local anesthetics with biomembranes consisting of phospholipids and cholesterol. Understanding the membrane interactivity of local anesthetics would provide novel insights into their anesthetic and cardiotoxic effects.

scholarly journals Fengycin induces ion channels in lipid bilayers mimicking target fungal cell membranes

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Anastasiia A. Zakharova ◽  
Svetlana S. Efimova ◽  
Valery V. Malev ◽  
Olga S. Ostroumova
Keyword(s):  
Ion Channels ◽  
Lipid Bilayers ◽  
Cell Membranes ◽  
Membrane Lipids ◽  
Electrical Potential ◽  
Membrane Conductance ◽  
Pressure Profile ◽  
Molecular Shape ◽  
Bathing Solution ◽  
Fungal Cell

Abstract The one-sided addition of fengycin (FE) to planar lipid bilayers mimicking target fungal cell membranes up to 0.1 to 0.5 μM in the membrane bathing solution leads to the formation of well-defined and well-reproducible single-ion channels of various conductances in the picosiemens range. FE channels were characterized by asymmetric conductance-voltage characteristic. Membranes treated with FE showed nonideal cationic selectivity in potassium chloride bathing solutions. The membrane conductance induced by FE increased with the second power of the lipopeptide aqueous concentration, suggesting that at least FE dimers are involved in the formation of conductive subunits. The pore formation ability of FE was not distinctly affected by the molecular shape of membrane lipids but strongly depended on the presence of negatively charged species in the bilayer. FE channels were characterized by weakly pronounced voltage gating. Small molecules known to modify the transmembrane distribution of electrical potential and the lateral pressure profile were used to modulate the channel-forming activity of FE. The observed effects of membrane modifiers were attributed to changes in lipid packing and lipopeptide oligomerization in the membrane.

Membrane lipid biogenesis and transport

1986 ◽  
Vol 44 ◽  
pp. 70-71
Author(s):  
E.A. Dawidowicz
Keyword(s):  
Lipid Bilayers ◽  
De Novo ◽  
Membrane Lipids ◽  
Essential Feature ◽  
Liver Microsomes ◽  
Eukaryotic Cell ◽  
Membrane Lipid ◽  
Membrane Components ◽  
Isolated Liver ◽  
Initial Assembly

Membrane biogenesis is an essential feature of cellular development and growth. The initial assembly of membrane lipids and proteins occurs primarily in the endoplasmic reticulum (ER). It has been demonstrated that the enzymes involved in the de novo biosynthesis of phospholipids are exclusively located on the cytoplasmic surface of the ER. A rapid transbilayer movement of phospholipids has also been reported in isolated liver microsomes, which is compatible with the movement of newly synthesized lipids to the lumenal surface of the ER. Comparison with the transbilayer movement of phospholipids across protein-free lipid bilayers, has lead to the proposal that a protein which would catalyze the translocation of phospholipids across the ER membrane (“flipase”), might be involved in the assembly of the lipid bilayer of the ER. Since the various membranes in a eukaryotic cell differ markedly in their lipid composition, it is clear that specific sorting and transport of these membrane components must occur.

scholarly journals Relation between the organization of spectrin and of membrane lipids in lymphocytes.

1988 ◽  
Vol 106 (3) ◽  
pp. 697-703 ◽  
Author(s):  
B J Del Buono ◽  
P L Williamson ◽  
R A Schlegel
Keyword(s):  
Lipid Bilayers ◽  
Blood Cells ◽  
Membrane Lipids ◽  
Peripheral Blood Lymphocytes ◽  
Membrane Lipid ◽  
Cytoskeletal Protein ◽  
Flow Cytometric ◽  
Merocyanine 540 ◽  
Lipid Organization ◽  
Flow Cytometric Sorting

In lymphocytes, the cytoskeletal protein spectrin exhibits two organizational states. Because the plasma membrane lipids of lymphocytes also display two organizational states, it was asked whether there is a relation between the organization of spectrin and of membrane lipids. When mouse thymocytes were stained with merocyanine 540 (MC540), a fluorescent lipophilic probe that binds preferentially to loosely packed, disorganized lipid bilayers, some cells fluoresced brightly and some only dimly or not at all. When the same population was stained for spectrin by indirect immunofluorescence, the spectrin in some cells was uniformly distributed, while in others it was concentrated in a unipolar aggregate. Techniques enriching for mature thymocytes selected for cells displaying low MC540 fluorescence and aggregated spectrin, the same characteristics found in peripheral blood lymphocytes. Flow cytometric sorting of thymocytes based on MC540 phenotype simultaneously sorted them by spectrin phenotype. Finally, treatment with agents that alter the distribution of spectrin caused mature lymphocytes to display high MC540 fluorescence and uniform spectrin. Thus, a relation exists between the organizational states of spectrin and of membrane lipids in lymphocytes: aggregated spectrin is found in cells with tightly organized membrane lipids, uniform spectrin in those with loosely organized lipids. Spectrin may thus be involved in modulating membrane lipid organization in lymphocytes as it is in erythrocytes. Since loosely organized lipids may promote adhesion of blood cells to reticuloendothelial cells, spectrin may thereby be involved in transducing an internally generated adhesion signal to the lymphocyte surface.

scholarly journals An Early Stage of Membrane Fusion Mediated by the Low pH Conformation of Influenza Hemagglutinin Depends upon Membrane Lipids

1997 ◽  
Vol 136 (1) ◽  
pp. 81-93 ◽  
Author(s):  
Leonid V. Chernomordik ◽  
Eugenia Leikina ◽  
Vadim Frolov ◽  
Peter Bronk ◽  
Joshua Zimmerberg
Keyword(s):  
Membrane Fusion ◽  
Lipid Bilayers ◽  
Cell Fusion ◽  
Membrane Lipids ◽  
Early Stage ◽  
Molecular Shape ◽  
Membrane Lipid ◽  
Low Ph ◽  
Fusion Pore ◽  
Influenza Hemagglutinin

While the specificity and timing of membrane fusion in diverse physiological reactions, including virus–cell fusion, is determined by proteins, fusion always involves the merger of membrane lipid bilayers. We have isolated a lipid-dependent stage of cell–cell fusion mediated by influenza hemagglutinin and triggered by cell exposure to mildly acidic pH. This stage preceded actual membrane merger and fusion pore formation but was subsequent to a low pH–induced change in hemagglutinin conformation that is required for fusion. A low pH conformation of hemagglutinin was required to achieve this lipid-dependent stage and also, downstream of it, to drive fusion to completion. The lower the pH of the medium applied to trigger fusion and, thus, the more hemagglutinin molecules activated, the less profound was the dependence of fusion on lipids. Membrane-incorporated lipids affected fusion in a manner that correlated with their dynamic molecular shape, a characteristic that determines a lipid monolayer's propensity to bend in different directions. The lipid sensitivity of this stage, i.e., inhibition of fusion by inverted cone–shaped lysophosphatidylcholine and promotion by cone-shaped oleic acid, was consistent with the stalk hypothesis of fusion, suggesting that fusion proteins begin membrane merger by promoting the formation of a bent, lipid-involving, stalk intermediate.

scholarly journals The Crucial Roles of Phospholipids in Aging and Lifespan Regulation

2021 ◽  
Vol 12 ◽  
Author(s):  
Yucan Dai ◽  
Haiqing Tang ◽  
Shanshan Pang
Keyword(s):  
Lipid Bilayers ◽  
Membrane Lipids ◽  
Membrane Lipid ◽  
Mechanisms Of Action ◽  
Cellular Processes ◽  
Physiological Processes ◽  
Lipid Change ◽  
The Relationship ◽  
Signal Transductions ◽  
Phospholipid Species

Phospholipids are major membrane lipids that consist of lipid bilayers. This basic cellular structure acts as a barrier to protect the cell against various environmental insults and more importantly, enables multiple cellular processes to occur in subcellular compartments. Numerous studies have linked the complexity of membrane lipids to signal transductions, organelle functions, as well as physiological processes, and human diseases. Recently, crucial roles for membrane lipids in the aging process are beginning to emerge. In this study, we summarized current advances in our understanding of the relationship between membrane lipids and aging with an emphasis on phospholipid species. We surveyed how major phospholipid species change with age in different organisms and tissues, and some common patterns of membrane lipid change during aging were proposed. Further, the functions of different phospholipid molecules in regulating healthspan and lifespan, as well as their potential mechanisms of action, were also discussed.

scholarly journals Lipid Remodeling Confers Osmotic Stress Tolerance to Embryogenic Cells during Cryopreservation

2021 ◽  
Vol 22 (4) ◽  
pp. 2174
Author(s):  
Liang Lin ◽  
Junchao Ma ◽  
Qin Ai ◽  
Hugh W. Pritchard ◽  
Weiqi Li ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Technology Development ◽  
Membrane Lipids ◽  
Species Conservation ◽  
Membrane Lipid ◽  
Cell Integrity ◽  
Embryogenic Cells ◽  
Osmotic Stress Tolerance ◽  
Lipid Species ◽  
Magnolia Officinalis

Plant species conservation through cryopreservation using plant vitrification solutions (PVS) is based in empiricism and the mechanisms that confer cell integrity are not well understood. Using ESI-MS/MS analysis and quantification, we generated 12 comparative lipidomics datasets for membranes of embryogenic cells (ECs) of Magnolia officinalis during cryogenic treatments. Each step of the complex PVS-based cryoprotocol had a profoundly different impact on membrane lipid composition. Loading treatment (osmoprotection) remodeled the cell membrane by lipid turnover, between increased phosphatidic acid (PA) and phosphatidylglycerol (PG) and decreased phosphatidylcholine (PC) and phosphatidylethanolamine (PE). The PA increase likely serves as an intermediate for adjustments in lipid metabolism to desiccation stress. Following PVS treatment, lipid levels increased, including PC and PE, and this effectively counteracted the potential for massive loss of lipid species when cryopreservation was implemented in the absence of cryoprotection. The present detailed cryobiotechnology findings suggest that the remodeling of membrane lipids and attenuation of lipid degradation are critical for the successful use of PVS. As lipid metabolism and composition varies with species, these new insights provide a framework for technology development for the preservation of other species at increasing risk of extinction.

scholarly journals Impact of Membrane Lipids on UapA and AzgA Transporter Subcellular Localization and Activity in Aspergillus nidulans

2021 ◽  
Vol 7 (7) ◽  
pp. 514
Author(s):  
Mariangela Dionysopoulou ◽  
George Diallinas
Keyword(s):  
Plasma Membrane ◽  
Subcellular Localization ◽  
Aspergillus Nidulans ◽  
Membrane Lipids ◽  
Membrane Lipid ◽  
Lipid Biosynthesis ◽  
Transport Kinetics ◽  
Negative Effect ◽  
And Function

Recent biochemical and biophysical evidence have established that membrane lipids, namely phospholipids, sphingolipids and sterols, are critical for the function of eukaryotic plasma membrane transporters. Here, we study the effect of selected membrane lipid biosynthesis mutations and of the ergosterol-related antifungal itraconazole on the subcellular localization, stability and transport kinetics of two well-studied purine transporters, UapA and AzgA, in Aspergillus nidulans. We show that genetic reduction in biosynthesis of ergosterol, sphingolipids or phosphoinositides arrest A. nidulans growth after germling formation, but solely blocks in early steps of ergosterol (Erg11) or sphingolipid (BasA) synthesis have a negative effect on plasma membrane (PM) localization and stability of transporters before growth arrest. Surprisingly, the fraction of UapA or AzgA that reaches the PM in lipid biosynthesis mutants is shown to conserve normal apparent transport kinetics. We further show that turnover of UapA, which is the transporter mostly sensitive to membrane lipid content modification, occurs during its trafficking and by enhanced endocytosis, and is partly dependent on autophagy and Hect-type HulARsp5 ubiquitination. Our results point out that the role of specific membrane lipids on transporter biogenesis and function in vivo is complex, combinatorial and transporter-dependent.

scholarly journals Lipid bilayer degradation induced by SARS-CoV-2 spike protein as revealed by neutron reflectometry

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Alessandra Luchini ◽  
Samantha Micciulla ◽  
Giacomo Corucci ◽  
Krishna Chaithanya Batchu ◽  
Andreas Santamaria ◽  
...  
Keyword(s):  
Lipid Bilayer ◽  
Lipid Bilayers ◽  
Membrane Lipids ◽  
Lipid Extraction ◽  
Specific Interaction ◽  
Structural Features ◽  
Supported Lipid Bilayers ◽  
Fusion Event ◽  
Angiotensin Converting Enzyme 2 ◽  
Neutron Reflection

AbstractSARS-CoV-2 spike proteins are responsible for the membrane fusion event, which allows the virus to enter the host cell and cause infection. This process starts with the binding of the spike extramembrane domain to the angiotensin-converting enzyme 2 (ACE2), a membrane receptor highly abundant in the lungs. In this study, the extramembrane domain of SARS-CoV-2 Spike (sSpike) was injected on model membranes formed by supported lipid bilayers in presence and absence of the soluble part of receptor ACE2 (sACE2), and the structural features were studied at sub-nanometer level by neutron reflection. In all cases the presence of the protein produced a remarkable degradation of the lipid bilayer. Indeed, both for membranes from synthetic and natural lipids, a significant reduction of the surface coverage was observed. Quartz crystal microbalance measurements showed that lipid extraction starts immediately after sSpike protein injection. All measurements indicate that the presence of proteins induces the removal of membrane lipids, both in the presence and in the absence of ACE2, suggesting that sSpike molecules strongly associate with lipids, and strip them away from the bilayer, via a non-specific interaction. A cooperative effect of sACE2 and sSpike on lipid extraction was also observed.

Membrane Lipids and Maximum Lifespan in Clownfish

2021 ◽  
Author(s):  
PEDRO FRANCISCO ALMAIDA PAGÁN ◽  
Alejandro Lucas-Sanchez ◽  
Antonio Martinez-Nicolas ◽  
Eva Terzibasi ◽  
Maria Angeles Rol de Lama ◽  
...  
Keyword(s):  
Lipid Composition ◽  
Potential Model ◽  
Membrane Lipids ◽  
Membrane Lipid ◽  
Maximum Lifespan ◽  
Homeoviscous Adaptation ◽  
Theory Of Aging ◽  
Peroxidation Index ◽  
Membrane Peroxidation ◽  
Contradictory Data

Abstract The longevity-homeoviscous adaptation (LHA) theory of aging states that lipid composition of cell membranes is linked to metabolic rate and lifespan, which has been widely shown in mammals and birds but not sufficiently in fish. In this study, two species of the genus Amphiprion (A. percula and A. clarkii, with estimated maximum lifespan potentials [MLSP] of 30 and 9-16 years, respectively) and the damselfish Chromis viridis (estimated MLSP of 1-2 years) were chosen to test the LHA theory of aging in a potential model of exceptional longevity. Brain, livers and samples of skeletal muscle were collected for lipid analyses and integral part in the computation of membrane peroxidation indexes (PIn) from phospholipid (PL) fractions and PL fatty acid composition. When only the two anemonefish were compared, results pointed to the existence of a negative correlation between membrane PIn value and maximum life expectancy, well in line with the predictions from the LHA theory of aging. Nevertheless, contradictory data were obtained when the two clownfish were compared to the shorter-lived C. viridis. This results along with those obtained in previous studies on fish denote that the magnitude (and sometimes the direction) of the differences observed in membrane lipid composition and peroxidation index with MLSP cannot explain alone the diversity in longevity found among fishes.

Do local anesthetics interact preferentially with membrane lipid rafts? Comparative interactivities with raft-like membranes

2010 ◽  
Vol 24 (4) ◽  
pp. 639-642 ◽  
Author(s):  
Hironori Tsuchiya ◽  
Takahiro Ueno ◽  
Maki Mizogami ◽  
Ko Takakura
Keyword(s):  
Lipid Rafts ◽  
Local Anesthetics ◽  
Membrane Lipid
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