1-palmitoyl-2-oleoylphosphatidylethanolamine and Hemolysis

1-palmitoyl-2-oleoylphosphatidylethanolamine has been researched along with Hemolysis* in 5 studies

Other Studies

5 other study(ies) available for 1-palmitoyl-2-oleoylphosphatidylethanolamine and Hemolysis

ArticleYear
Delineating residues for haemolytic activities of snake venom cardiotoxin 1 from Naja naja as probed by molecular dynamics simulations and in vitro validations.
    International journal of biological macromolecules, 2017, Volume: 95

    Cardiotoxins (CTXs) are single polypeptide chain consisting of 59-62 amino acids with four disulfide bridges and globular proteins of simple β-sheet folds. The CTXs are one of principal toxic components causing haemolysis and damaging various cells and belong to three-finger toxin (TFT) superfamily of snake venoms. However, there is no natural or synthetic small molecular inhibitor to the protein toxins to date. In the present study, modes of interaction of cardiotoxin 1 (CTX1) from Indian cobra (Naja naja) with heterogeneous erythrocyte membrane (EM) model system have been extensively examined by using all-atom molecular dynamics (MD) simulations in near physiological conditions and comprehensive analyses of the MD data revealed two distinct principal regions ('head groove' and 'loop groove') of the protein toxin for establishing structural interactions with the EM system. Moreover, combined analyses of data from high-throughput virtual screening of NCI small molecular database, in vitro haemolytic assays for top-hits of the chemical compounds against crude venom of Naja naja and as well CTXs purified from the venom and pharmacokinetic examinations on the chemical compounds retarding haemolytic activities of CTXs suggested that Etidronic acid and Zoledronic acid are promising prototypic chemical inhibitors to CTXs of snake venoms.

    Topics: Amino Acid Sequence; Animals; Antidotes; Cholesterol; Cobra Cardiotoxin Proteins; Diphosphonates; Disulfides; Elapid Venoms; Elapidae; Erythrocyte Membrane; Etidronic Acid; Hemolysis; High-Throughput Screening Assays; Humans; Imidazoles; Molecular Dynamics Simulation; Phosphatidylcholines; Phosphatidylethanolamines; Phosphatidylserines; Protein Domains; Protein Structure, Secondary; Small Molecule Libraries; Structure-Activity Relationship; User-Computer Interface; Zoledronic Acid

2017
Kinetic and Structural Aspects of the Permeabilization of Biological and Model Membranes by Lichenysin.
    Langmuir : the ACS journal of surfaces and colloids, 2016, Jan-12, Volume: 32, Issue:1

    The various lichenysins produced by Bacillus licheniformis are anionic surfactants with interesting properties. Here it is shown that lichenysin caused hemolysis of human erythrocytes, which varied with lichenysin concentration in a sigmoidal manner. The release of K(+) from red blood cells induced by lichenysin preceded the leakage of hemoglobin, and in addition, hemolysis could be impeded by the presence of compounds in the external medium having a size larger than that of PEG 3350, indicating a colloid-osmotic mechanism for hemolysis. Lichenysin also caused permeabilization of model phospholipid membranes, which was a slow process with an initial lag period of 10-20 s observed for all lichenysin concentrations. A high cholesterol ratio in the membrane decreased the extent of leakage as compared to that of pure POPC, whereas at lower ratios the effect of cholesterol was the opposite, enhancing the extent of leakage. POPE was found to decrease the extent of leakage at all the concentrations assayed, and inclusion of DPPC resulted in a considerable increase in CF leakage extent. From this scenario it was concluded that lipid membrane composition plays a role in the target membrane selectivity of lichenysin. Molecular dynamics simulations indicated that lichenysin is well distributed along the bilayer, and Na(+) ions can penetrate inside the bilayer through the lichenysin molecules. The presence of lichenysin in the membrane increases the permeability of the membrane to hydrophilic molecules facilitating its flux across the lipid palisade. The results presented in this work contribute to understanding the molecular mechanisms that explain the biological actions of lichenysin related to biomembranes.

    Topics: Erythrocytes; Hemolysis; Humans; Kinetics; Lipid Bilayers; Lipoproteins; Molecular Dynamics Simulation; Permeability; Phosphatidylethanolamines; Surface-Active Agents

2016
Bacteria May Cope Differently from Similar Membrane Damage Caused by the Australian Tree Frog Antimicrobial Peptide Maculatin 1.1.
    The Journal of biological chemistry, 2015, Aug-07, Volume: 290, Issue:32

    Maculatin 1.1 (Mac1) is an antimicrobial peptide from the skin of Australian tree frogs and is known to possess selectivity toward Gram-positive bacteria. Although Mac1 has membrane disrupting activity, it is not known how Mac1 selectively targets Gram-positive over Gram-negative bacteria. The interaction of Mac1 with Escherichia coli, Staphylococcus aureus, and human red blood cells (hRBC) and with their mimetic model membranes is here reported. The peptide showed a 16-fold greater growth inhibition activity against S. aureus (4 μM) than against E. coli (64 μM) and an intermediate cytotoxicity against hRBC (30 μM). Surprisingly, Sytox Green uptake monitored by flow cytometry showed that Mac1 compromised both bacterial membranes with similar efficiency at ∼20-fold lower concentration than the reported minimum inhibition concentration against S. aureus. Mac1 also reduced the negative potential of S. aureus and E. coli membrane with similar efficacy. Furthermore, liposomes mimicking the cell membrane of S. aureus (POPG/TOCL) and E. coli (POPE/POPG) were lysed at similar concentrations, whereas hRBC-like vesicles (POPC/SM/Chol) remained mostly intact in the presence of Mac1. Remarkably, when POPG/TOCL and POPE/POPG liposomes were co-incubated, Mac1 did not induce leakage from POPE/POPG liposomes, suggesting a preference toward POPG/TOCL membranes that was supported by surface plasma resonance assays. Interestingly, circular dichroism spectroscopy showed a similar helical conformation in the presence of the anionic liposomes but not the hRBC mimics. Overall, the study showed that Mac1 disrupts bacterial membranes in a similar fashion before cell death events and would preferentially target S. aureus over E. coli or hRBC membranes.

    Topics: Amphibian Proteins; Animals; Antimicrobial Cationic Peptides; Anura; Cardiolipins; Cell Membrane; Cholesterol; Dose-Response Relationship, Drug; Erythrocytes; Escherichia coli; Hemolysis; Humans; Liposomes; Phosphatidylcholines; Phosphatidylethanolamines; Phosphatidylglycerols; Species Specificity; Sphingomyelins; Staphylococcus aureus

2015
Engineering antimicrobial peptides with improved antimicrobial and hemolytic activities.
    Journal of chemical information and modeling, 2013, Dec-23, Volume: 53, Issue:12

    The rapid rise of antibiotic resistance in pathogens becomes a serious and growing threat to medicine and public health. Naturally occurring antimicrobial peptides (AMPs) are an important line of defense in the immune system against invading bacteria and microbial infection. In this work, we present a combined computational and experimental study of the biological activity and membrane interaction of the computationally designed Bac2A-based peptide library. We used the MARTINI coarse-grained molecular dynamics with adaptive biasing force method and the umbrella sampling technique to investigate the translocation of a total of 91 peptides with different amino acid substitutions through a mixed anionic POPE/POPG (3:1) bilayer and a neutral POPC bilayer, which mimic the bacterial inner membrane and the human red blood cell (hRBC) membrane, respectively. Potential of mean force (PMF, free energy profile) was obtained to measure the free energy barrier required to transfer the peptides from the bulk water phase to the water-membrane interface and to the bilayer interior. Different PMF profiles can indeed identify different membrane insertion scenarios by mapping out peptide-lipid energy landscapes, which are correlated with antimicrobial activity and hemolytic activity. Computationally designed peptides were further tested experimentally for their antimicrobial and hemolytic activities using bacteria growth inhibition assay and hemolysis assay. Comparison of PMF data with cell assay results reveals a good correlation of the peptides between predictive transmembrane activity and antimicrobial/hemolytic activity. Moreover, the most active mutants with the balanced substitutions of positively charged Arg and hydrophobic Trp residues at specific positions were discovered to achieve the improved antimicrobial activity while minimizing red blood cell lysis. Such substitutions provide more effective and cooperative interactions to distinguish the peptide interaction with different lipid bilayers. This work provides a useful computational tool to better understand the mechanism and energetics of membrane insertion of AMPs and to rationally design more effective AMPs.

    Topics: Amino Acid Sequence; Amino Acid Substitution; Antimicrobial Cationic Peptides; Biological Transport; Cell Membrane; Diffusion; Hemolysis; Humans; Hydrophobic and Hydrophilic Interactions; Lipid Bilayers; Microbial Sensitivity Tests; Molecular Dynamics Simulation; Molecular Mimicry; Molecular Sequence Data; Peptide Library; Phosphatidylcholines; Phosphatidylethanolamines; Phosphatidylglycerols; Protein Engineering; Pseudomonas aeruginosa; Thermodynamics

2013
Permeabilization of biological and artificial membranes by a bacterial dirhamnolipid produced by Pseudomonas aeruginosa.
    Journal of colloid and interface science, 2010, Jan-15, Volume: 341, Issue:2

    Pseudomonas aeruginosa, when cultured under the appropriate conditions, secretes rhamnolipids to the external medium. These glycolipids constitute one of the most interesting classes of biosurfactants so far. A dirhamnolipid fraction was isolated and purified from the crude biosurfactant, and its action on model and biological membranes was studied. Dirhamnolipid induced leakage of internal contents, as measured by the release of carboxyfluorescein, in phosphatidylcholine unilamellar vesicles, at concentrations below its CMC. Membrane solubilization was not observed within this concentration range. The presence of inverted cone-shaped lipids in the membrane, namely lysophosphatidylcholine, accelerated leakage, whereas cone-shaped lipids, like phosphatidylethanolamine, decreased leakage rate. Increasing concentrations of cholesterol protected the membrane against dirhamnolipid-induced leakage, which was totally abolished by the presence of 50 mol% of the sterol. Dirhamnolipid caused hemolysis of human erythrocytes through a lytic mechanism, as shown by the similar rates of K(+) and hemoglobin leakage, and by the absence of effect of osmotic protectants. Scanning electron microscopy showed that the addition of the biosurfactant changed the usual disc shape of erythrocytes into that of spheroechinocytes. The results are discussed within the frame of the biological actions of dirhamnolipid, and the possible future applications of this biosurfactant.

    Topics: Cell Membrane; Cell Shape; Cholesterol; Erythrocytes; Fluoresceins; Glycolipids; Hemoglobins; Hemolysis; Humans; Kinetics; Lysophosphatidylcholines; Membranes, Artificial; Permeability; Phosphatidylcholines; Phosphatidylethanolamines; Polyethylene Glycols; Potassium; Pseudomonas aeruginosa; Unilamellar Liposomes

2010