scholarly journals Fibril Formation by Glucagon in Solution and in Membrane Environments

2020 ◽  
Author(s):  
Akira Naito
Keyword(s):  
Lipid Bilayers ◽  
Structural Changes ◽  
Acidic Solution ◽  
Peptide Hormone ◽  
Fibril Formation ◽  
Amino Acid Peptide ◽  
Specific Receptors ◽  
Dmpc Bilayer ◽  
Elongation Process ◽  
Fibril Aggregates

Glucagon is a 29-amino acid peptide hormone secreted by pancreatic α-cells and interacts with specific receptors located in various organs. Glucagon tends to form gel-like fibril aggregates that are cytotoxic because they activate apoptotic signaling pathways. First, fibril formation by glucagon in acidic solution is discussed in light of morphological and structural changes during elapsed time. Second, we provide kinetic analyses using a two-step autocatalytic reaction mechanism; the first step is a homogeneous nuclear formation process, and the second step is an autocatalytic heterogeneous fibril elongation process. Third, the processes of fibril formation by glucagon in a membrane environment are discussed based on the structural changes in the fibrils. In the presence of bicelles in acidic solution, glucagon interacts with the bicelles and forms fibril intermediates on the bicelle surface and grows into elongated fibrils. Glucagon-dimyristoylphosphatidylcholine (DMPC) bilayers in neutral solution mimic the environment for fibril formation by glucagon under near-physiological condition. Under these conditions, glucagon forms fibril intermediates that grow into elongated fibrils inside the lipid bilayer. Many days after preparing the glucagon-DMPC bilayer sample, the fibrils form networks inside and outside the bilayer. Furthermore, fibril intermediates strongly interact with lipid bilayers to form small particles.

scholarly journals The Structural Integrity of the Model Lipid Membrane during Induced Lipid Peroxidation: The Role of Flavonols in the Inhibition of Lipid Peroxidation

Antioxidants ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 430 ◽  
Author(s):  
Anja Sadžak ◽  
Janez Mravljak ◽  
Nadica Maltar-Strmečki ◽  
Zoran Arsov ◽  
Goran Baranović ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Lipid Bilayers ◽  
Lipid Membranes ◽  
Structural Changes ◽  
Structural Integrity ◽  
Lipid Membrane ◽  
Membrane Properties ◽  
Structural Reorganization ◽  
Unsaturated Lipids ◽  
Oxidative Attack

The structural integrity, elasticity, and fluidity of lipid membranes are critical for cellular activities such as communication between cells, exocytosis, and endocytosis. Unsaturated lipids, the main components of biological membranes, are particularly susceptible to the oxidative attack of reactive oxygen species. The peroxidation of unsaturated lipids, in our case 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), induces the structural reorganization of the membrane. We have employed a multi-technique approach to analyze typical properties of lipid bilayers, i.e., roughness, thickness, elasticity, and fluidity. We compared the alteration of the membrane properties upon initiated lipid peroxidation and examined the ability of flavonols, namely quercetin (QUE), myricetin (MCE), and myricitrin (MCI) at different molar fractions, to inhibit this change. Using Mass Spectrometry (MS) and Fourier Transform Infrared Spectroscopy (FTIR), we identified various carbonyl products and examined the extent of the reaction. From Atomic Force Microscopy (AFM), Force Spectroscopy (FS), Small Angle X-Ray Scattering (SAXS), and Electron Paramagnetic Resonance (EPR) experiments, we concluded that the membranes with inserted flavonols exhibit resistance against the structural changes induced by the oxidative attack, which is a finding with multiple biological implications. Our approach reveals the interplay between the flavonol molecular structure and the crucial membrane properties under oxidative attack and provides insight into the pathophysiology of cellular oxidative injury.

The Physiology of Glucagon-like Peptide 1

2007 ◽  
Vol 87 (4) ◽  
pp. 1409-1439 ◽  
Author(s):  
Jens Juul Holst
Keyword(s):  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Glucagon Secretion ◽  
Peptide Hormone ◽  
Postprandial Glucose ◽  
Cell Secretion ◽  
Amino Acid Peptide ◽  
Reactive Hypoglycemia ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Glucagon-like peptide 1 (GLP-1) is a 30-amino acid peptide hormone produced in the intestinal epithelial endocrine L-cells by differential processing of proglucagon, the gene which is expressed in these cells. The current knowledge regarding regulation of proglucagon gene expression in the gut and in the brain and mechanisms responsible for the posttranslational processing are reviewed. GLP-1 is released in response to meal intake, and the stimuli and molecular mechanisms involved are discussed. GLP-1 is extremely rapidly metabolized and inactivated by the enzyme dipeptidyl peptidase IV even before the hormone has left the gut, raising the possibility that the actions of GLP-1 are transmitted via sensory neurons in the intestine and the liver expressing the GLP-1 receptor. Because of this, it is important to distinguish between measurements of the intact hormone (responsible for endocrine actions) or the sum of the intact hormone and its metabolites, reflecting the total L-cell secretion and therefore also the possible neural actions. The main actions of GLP-1 are to stimulate insulin secretion (i.e., to act as an incretin hormone) and to inhibit glucagon secretion, thereby contributing to limit postprandial glucose excursions. It also inhibits gastrointestinal motility and secretion and thus acts as an enterogastrone and part of the “ileal brake” mechanism. GLP-1 also appears to be a physiological regulator of appetite and food intake. Because of these actions, GLP-1 or GLP-1 receptor agonists are currently being evaluated for the therapy of type 2 diabetes. Decreased secretion of GLP-1 may contribute to the development of obesity, and exaggerated secretion may be responsible for postprandial reactive hypoglycemia.

scholarly journals Topological analysis of the gp41 MPER on lipid bilayers relevant to the metastable HIV-1 envelope prefusion state

2019 ◽  
Vol 116 (45) ◽  
pp. 22556-22566 ◽  
Author(s):  
Yi Wang ◽  
Pavanjeet Kaur ◽  
Zhen-Yu J. Sun ◽  
Mostafa A. Elbahnasawy ◽  
Zahra Hayati ◽  
...  
Keyword(s):  
Lipid Bilayers ◽  
Neutralizing Antibodies ◽  
Structural Changes ◽  
Transmembrane Domain ◽  
Topological Analysis ◽  
Heptad Repeat ◽  
Structural Topology ◽  
Paramagnetic Resonance ◽  
Viral Membrane ◽  
Hiv 1

The membrane proximal external region (MPER) of HIV-1 envelope glycoprotein (gp) 41 is an attractive vaccine target for elicitation of broadly neutralizing antibodies (bNAbs) by vaccination. However, current details regarding the quaternary structural organization of the MPER within the native prefusion trimer [(gp120/41)3] are elusive and even contradictory, hindering rational MPER immunogen design. To better understand the structural topology of the MPER on the lipid bilayer, the adjacent transmembrane domain (TMD) was appended (MPER-TMD) and studied. Membrane insertion of the MPER-TMD was sensitive both to the TMD sequence and cytoplasmic residues. Antigen binding of MPER-specific bNAbs, in particular 10E8 and DH511.2_K3, was significantly impacted by the presence of the TMD. Furthermore, MPER-TMD assembly into 10-nm diameter nanodiscs revealed a heterogeneous membrane array comprised largely of monomers and dimers, as enumerated by bNAb Fab binding using single-particle electron microscopy analysis, arguing against preferential trimeric association of native MPER and TMD protein segments. Moreover, introduction of isoleucine mutations in the C-terminal heptad repeat to induce an extended MPER α-helical bundle structure yielded an antigenicity profile of cell surface-arrayed Env variants inconsistent with that found in the native prefusion state. In line with these observations, electron paramagnetic resonance analysis suggested that 10E8 inhibits viral membrane fusion by lifting the MPER N-terminal region out of the viral membrane, mandating the exposure of residues that would be occluded by MPER trimerization. Collectively, our data suggest that the MPER is not a stable trimer, but rather a dynamic segment adapted for structural changes accompanying fusion.

scholarly journals AFM nanoindentation reveals decrease of elastic modulus of lipid bilayers near freezing point of water

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Calum Gabbutt ◽  
Wuyi Shen ◽  
Jacob Seifert ◽  
Sonia Contera
Keyword(s):  
Lipid Bilayers ◽  
Lipid Membranes ◽  
Structural Changes ◽  
Freezing Point ◽  
Liquid Environment ◽  
Force Microscopy ◽  
Atomic Force ◽  
Afm Imaging ◽  
Underlying Causes ◽  
Irreversible Injury

AbstractCell lipid membranes are the primary site of irreversible injury during freezing/thawing and cryopreservation of cells, but the underlying causes remain unknown. Here, we probe the effect of cooling from 20 °C to 0 °C on the structure and mechanical properties of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) bilayers using atomic force microscopy (AFM) imaging and AFM-based nanoindentation in a liquid environment. The Young’s modulus of elasticity (E) at each temperature for DPPC was obtained at different ionic strengths. Both at 20 mM and 150 mM NaCl, E of DPPC bilayers increases exponentially –as expected–as the temperature is lowered between 20 °C and 5 °C, but at 0 °C E drops from the values measured at 5 °C. Our results support the hypothesis that mechanical weakening of the bilayer at 0 °C  is produced by  structural changes at the lipid-fluid interface.

scholarly journals The effect of acid mucopolysaccharides and acid mucopolysaccharide–proteins on fibril formation from collagen solutions

1968 ◽  
Vol 109 (4) ◽  
pp. 517-526 ◽  
Author(s):  
M B Mathews ◽  
L. Decker
Keyword(s):  
Molecular Weight ◽  
Light Scattering ◽  
High Molecular Weight ◽  
Chondroitin Sulphate ◽  
Fibril Formation ◽  
Acid Mucopolysaccharide ◽  
Acid Mucopolysaccharides ◽  
Electrostatic Binding ◽  
Fibril Aggregates ◽  
Chondroitin Sulphate A

1. The effects of acid mucopolysaccharides and acid mucopolysaccharide–proteins on the size and rate of formation of fibril aggregates from collagen solutions in pH7·6 buffers were studied by turbidimetric and light-scattering methods. 2. Serum albumin, orosomucoid, methylated cellulose, chondroitin sulphate A and chondroitin sulphate C of molecular weight less than 20000, and hyaluronate of molecular weight less than 40000 did not influence rates of fibril formation. Chondroitin sulphate A, chondroitin sulphate C and hyaluronate of high molecular weight retarded the rate of fibril formation. This effect of high-molecular-weight chondroitin sulphate C decreased with increasing ionic strength. Heparin, though of low molecular weight (13000), was highly effective, as was also heparitin sulphate. The chondroitin sulphate–proteins of very high molecular weight were highly effective, despite the fact that for some preparations the component chondroitin sulphate chains had molecular weights much less than 20000. 3. Agents that had delayed fibril formation were also effective in producing an increase in degree of aggregation of fibrillar collagen, as indicated by dissymmetry changes observed in light-scattering experiments at low collagen concentrations. Methylated cellulose and heparin at 2·5μg./ml. were unusual in decreasing aggregation, but heparin at 0·25μg./ml. increased aggregation. Electron microscopy of gels showed fibrils and fibril aggregates with ‘normal’ collagen spacing and dimensions consistent with the light-scattering results. 4. The rates of electrical transport of agents and of solvent (electro-osmosis) through collagen gels indicated a contribution of molecular entanglement that increased with increase in molecular size of the agents. Electrostatic binding of heparin to collagen was noted. Binding to collagen during fibril formation was also found for heparitin sulphate and a chondroitin sulphate with extra sulphate groups. 5. Electrostatic binding of acid mucopolysaccharide–proteins to collagen may be an important factor in the organization and functioning of connective tissues at all stages of growth and development. Excluded-volume (molecular-entanglement) effects may also be important. These factors operate simultaneously and interact mutually so that precise assessment of their relative importance is difficult.

Resonance Raman Spectroscopic Measurements Delineate the Structural Changes that Occur during Tau Fibril Formation

Biochemistry ◽  
2014 ◽  
Vol 53 (41) ◽  
pp. 6550-6565 ◽  
Author(s):  
Gayathri Ramachandran ◽  
Erix A. Milán-Garcés ◽  
Jayant B. Udgaonkar ◽  
Mrinalini Puranik
Keyword(s):  
Structural Changes ◽  
Resonance Raman ◽  
Fibril Formation ◽  
Spectroscopic Measurements ◽  
Raman Spectroscopic

scholarly journals Spexin and a novel cichlid-specific spexin paralog both inhibit FSH and LH through a specific galanin receptor (Galr2b) in tilapia

2019 ◽  
Author(s):  
Yaron Cohen ◽  
Krist Hausken ◽  
Yoav Bonfil ◽  
Michael Gutnick ◽  
Berta Levavi-Sivan
Keyword(s):  
Mammalian Species ◽  
Cichlid Fish ◽  
Peptide Hormone ◽  
Distribution Patterns ◽  
Cichlid Species ◽  
Amino Acid Peptide ◽  
Lh Cells ◽  
Pleiotropic Functions

AbstractSpexin (SPX) is a 14 amino acid peptide hormone that has pleiotropic functions across vertebrates, one of which is involvement in the brain-pituitary-gonad axis of fish. SPX(1) has been identified in each class of vertebrates, and a second SPX (named SPX2) has been found in some non-mammalian species. We have cloned two spexin paralogs, designated as Spx1a and Spx1b, from Nile tilapia (Oreochromis niloticus) that have varying tissue distribution patterns. Spx1b is a novel peptide only identified in cichlid fish, and is more closely related to Spx1 than Spx2 homologs as supported by phylogenetic, synteny, and functional analyses. Kisspeptin, Spx, and galanin (Gal) peptides and their corresponding kiss receptors and Gal receptors (Galrs), respectively, are evolutionarily related. Cloning of six tilapia Galrs (Galr1a, Galr1b, Galr2a, Galr2b, Galr type 1, and Galr type 2) and subsequent in vitro second-messenger reporter assays for Gαs, Gαq, and Gαi suggests that Gal and Spx activate Galr1a/Galr2a and Galr2b, respectively. A decrease in plasma follicle stimulating hormone and luteinizing hormone concentrations was observed with injections of Spx1a or Spx1b in vivo. Additionally, application of Spx1a to pituitary slices decreased the firing rate of LH cells, suggesting direct inhibition at the pituitary level. These data collectively suggest an inhibitory mechanism of action against the secretion of gonadotropins for a traditional and a novel spexin paralog in cichlid species.

scholarly journals Oxytocin as a Metabolic Modulator

2021 ◽  
Author(s):  
Neeru Bhatt
Keyword(s):  
Diabetes Mellitus ◽  
Enzyme Activity ◽  
Developmental Trajectories ◽  
Sugar Metabolism ◽  
Peptide Hormone ◽  
Endocrine Disorders ◽  
Metabolic Hormones ◽  
Amino Acid Peptide ◽  
G Protein Coupled ◽  
Receptor Family

Oxytocin (9-amino acid peptide) hormone is a member of the G-protein coupled receptor family. It regulates a range of physiologic actions in mammals other than assisting parturition and lactation functions. Evidence indicates that oxytocin alters lipids, protein, and sugar metabolism through various ways including modulation of appetite and satiety, enzyme activity, cellular signals, secretion of metabolic hormones, and energy consumption. Alterations in these processes have the potential to shift developmental trajectories and influence disease processes. Oxytocin can be a potential avenue for the treatment of endocrine disorders such as obesity, diabetes mellitus, and associated disorders. The chapter will include a comprehensive study about oxytocin and its physiological and pathological functions, which makes it a potential target for drug therapy.

Asymmetry of Structural Characteristics of Lipid Bilayers Induced by Dimethylsulfoxide: An Atomistic Simulation Study

2008 ◽  
Author(s):  
Raghava Alapati ◽  
Dorel Moldovan ◽  
Ram V. Devireddy
Keyword(s):  
Molecular Dynamics ◽  
Lipid Bilayers ◽  
Cell Biology ◽  
Cell Membranes ◽  
Structural Changes ◽  
Cell Damage ◽  
Structural Characteristics ◽  
Cellular Systems ◽  
Freezing Process ◽  
Cryopreservation Protocol

In a typical cryopreservation protocol, the system to be preserved is first equilibrated with chemicals known as cryoprotective agents (CPAs). CPAs have been shown to alleviate cell damage from either the solute effects or the formation of intracellular ice during the subsequent freezing process. Thus, an extensive body of literature reporting the effects of CPAs on cellular systems has been accumulated over the last 50 years; detailing largely experimental interactions between cell systems and chemicals. Recent advances in computational methodology now offer an additional dimension in our ability to understand the molecular interactions between cell membranes, idealized as lipid bilayers and CPAs at atomistic scales. Computer simulations provide unique capabilities for analyzing biomembrane properties from atomistic perspective with a degree of detail that is hard to reach by other techniques. The excellent agreement with the experiment obtained in various molecular dynamics (MD) studies [1] on simple model membranes has raised the confidence in applying the molecular dynamics simulations to even more complex systems. Dimethylsulfoxide (DMSO) is one of the most widely used solvents in cell biology and cryopreservation. During a typical cryopreservation protocol the DMSO composition of aqueous buffers inside and outside of the cell is known to differ considerably. To model and understand the structural changes in cell membranes in such a situation we performed MD simulations of an idealized lipid bilayer membrane which separates two aqueous reservoirs with and without DMSO. Zwitterionic dimyritoylphosphatidylcholine (DMPC) lipid bilayers was chosen as the model membrane.

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