Effect of different drugs on a cytochrome c – phospholipid bilayer membrane

1978 ◽  
Vol 56 (4) ◽  
pp. 555-563
Author(s):  
Michael A. Singer
Keyword(s):  
Cytochrome C ◽  
Protein Binding ◽  
Lipid Vesicles ◽  
Bilayer Membrane ◽  
Fatty Acyl ◽  
Phospholipid Bilayer ◽  
Butylated Hydroxytoluene ◽  
Na Permeability ◽  
Na Efflux ◽  
Temperature Interaction

Liposomes were prepared from dipalmitoyl phosphatidylcholine and dicetylphosphate and their interaction with the extrinsic membrane protein cytochrome c examined in terms of changes in 22Na permeability, electrophoretic mobility, protein binding, and motion of an incorporated spin label. The amount of cytochrome c bound displays no significant temperature dependence over the temperature range studied (from 30 to 55 °C) whereas cytochrome c causes an increase in 22Na efflux only above the phospholipid phase transition temperature. Interaction of the protein with the lipid vesicles causes no significant disturbance in the bilayer interior as monitored by the motion of the incorporated spin probe. The drugs 2,4-dinitrophenol and ethacrynic acid, both of which increase the magnitude of the vesicle negative charge, enhance both cytochrome c binding and its effect on 22Na permeability. In contrast, the local anesthetic dibucaine, which induces a positive surface charge on these liposomes, reduces both protein binding and the protein-induced increase in 22Na efflux. Finally, the chemicals butylated hydroxytoluene, 2-tert-butylphenol, and tert-butylbenzene, all of which cause early 'melting' of the phospholipid fatty acyl chains, block the capacity of cytochrome c to enhance 22Na permeability while having no effect on its binding to the vesicles.

scholarly journals Evaluation of the correlation between porphyrin accumulation in cancer cells and functional positions for application as a drug carrier

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Koshi Nishida ◽  
Toshifumi Tojo ◽  
Takeshi Kondo ◽  
Makoto Yuasa
Keyword(s):  
Cancer Cells ◽  
Drug Carrier ◽  
Bilayer Membrane ◽  
Phospholipid Bilayer ◽  
Membrane Permeation ◽  
Porphyrin Derivatives ◽  
Phospholipid Bilayer Membrane ◽  
Meso Position ◽  
Tumor Accumulation ◽  
Binding Position

AbstractPorphyrin derivatives accumulate selectively in cancer cells and are can be used as carriers of drugs. Until now, the substituents that bind to porphyrins (mainly at the meso-position) have been actively investigated, but the effect of the functional porphyrin positions (β-, meso-position) on tumor accumulation has not been investigated. Therefore, we investigated the correlation between the functional position of substituents and the accumulation of porphyrins in cancer cells using cancer cells. We found that the meso-derivative showed higher accumulation in cancer cells than the β-derivative, and porphyrins with less bulky substituent actively accumulate in cancer cells. When evaluating the intracellular distribution of porphyrin, we found that porphyrin was internalized by endocytosis and direct membrane permeation. As factors involved in these two permeation mechanisms, we evaluated the affinity between porphyrin-protein (endocytosis) and the permeability to the phospholipid bilayer membrane (direct membrane permeation). We found that the binding position of porphyrin affects the factors involved in the transmembrane permeation mechanisms and impacts the accumulation in cancer cells.

Bilayer Membrane Bending Stiffness by Tether Formation From Mixed PC-PS Lipid Vesicles

1990 ◽  
Vol 112 (3) ◽  
pp. 235-240 ◽  
Author(s):  
J. Song ◽  
R. E. Waugh
Keyword(s):  
Present Report ◽  
Membrane Surface ◽  
Lipid Vesicles ◽  
Phosphatidyl Serine ◽  
Bilayer Membrane ◽  
Bending Stiffness ◽  
New Approach ◽  
Lipid Mixtures ◽  
Membrane Bending ◽  
Membrane Surface Charge

Recently, a new approach to measure the bending stiffness (curvature elastic modulus) of lipid bilayer membrane was developed (Biophys. J., Vol. 55; pp. 509–517, 1989). The method involves the formation of cylindrical membrane strands (tethers) from bilayer vesicles. The bending stiffness (B) can be calculated from measurements of the tether radius (Rt) as a function of the axial force (f) on the tether: B =f·Rt/2π. In the present report, we apply this method to determine the bending stiffness of bilayer membranes composed of mixtures of SOPC (1-stearoyl-2-oleoyl phosphatidyl choline) and POPS (1-palmitoyl-2-oleoyl phosphatidyl serine). Three different mixtures were tested: pure SOPC, SOPC plus 2 percent (mol/mol) POPS, and SOPC plus 16 percent POPS. The bending stiffness determined for these three different lipid mixtures were not significantly different (1.6–1.8×10-12 ergs). Because POPS carries a net negative charge, these results indicate that changes in the density of the membrane surface charge have no effect on the intrinsic rigidity of the membrane. The values we obtain are consistent with published values for the bending stiffness of other membranes determined by different methods. Measurements of the aspiration pressure, the tether radius and the tether force were used to verify a theoretical relationship among these quantities at equilibrium. The ratio of the theoretical force to the measured force was 1.12 ± 0.17.

Synthetic, Sodium-Ion-Conducting Tris(Macrocycle) Channels that Function in a Phospholipid Bilayer Membrane: An Overview

2000 ◽  
Vol 12 (1) ◽  
pp. 13-22
Author(s):  
Stephen L. De Wall ◽  
Eric S. Meadows ◽  
Clare L. Murray ◽  
Hossein Shabany ◽  
George W. Gokel
Keyword(s):  
Bilayer Membrane ◽  
Sodium Ion ◽  
Phospholipid Bilayer ◽  
Phospholipid Bilayer Membrane ◽  
Ion Conducting

Interaction of triblock co-polymer micelles with phospholipid-bilayer: a spectroscopic investigation using a potential chloride channel blocker

2015 ◽  
Vol 17 (9) ◽  
pp. 6597-6605 ◽  
Author(s):  
Aniruddha Ganguly ◽  
Soumen Ghosh ◽  
Nikhil Guchhait
Keyword(s):  
Chloride Channel ◽  
Spectroscopic Investigation ◽  
Channel Blocker ◽  
Lipid Vesicles ◽  
Experimental Results ◽  
Phospholipid Bilayer ◽  
Polymer Micelles ◽  
Binding Interaction ◽  
Chloride Channel Blocker ◽  
Egg Pc

Experimental results reveal that addition of P123 to the drug-bound egg-PC vesicles results in a preferential complexation of the drug with the Pluronic leaving the lipid vesicles aside which indicates a substantially stronger binding interaction of the drug with P123 than that with egg-PC.

scholarly journals Identification of a translocated gating charge in a voltage-dependent channel. Colicin E1 channels in planar phospholipid bilayer membranes.

1991 ◽  
Vol 98 (1) ◽  
pp. 77-93 ◽  
Author(s):  
C K Abrams ◽  
K S Jakes ◽  
A Finkelstein ◽  
S L Slatin
Keyword(s):  
Voltage Dependence ◽  
Ion Selectivity ◽  
Lipid Vesicles ◽  
Voltage Gating ◽  
Site Directed Mutagenesis ◽  
Phospholipid Bilayer ◽  
Voltage Gated ◽  
Colicin E1 ◽  
Gating Charge ◽  
Ion Conducting

The availability of primary sequences for ion-conducting channels permits the development of testable models for mechanisms of voltage gating. Previous work on planar phospholipid bilayers and lipid vesicles indicates that voltage gating of colicin E1 channels involves translocation of peptide segments of the molecule into and across the membrane. Here we identify histidine residue 440 as a gating charge associated with this translocation. Using site-directed mutagenesis to convert the positively charged His440 to a neutral cysteine, we find that the voltage dependence for turn-off of channels formed by this mutant at position 440 is less steep than that for wild-type channels; the magnitude of the change in voltage dependence is consistent with residue 440 moving from the trans to the cis side of the membrane in association with channel closure. The effect of trans pH changes on the ion selectivity of channels formed by the carboxymethylated derivative of the cysteine 440 mutant independently establishes that in the open channel state, residue 440 lies on the trans side of the membrane. On the basis of these results, we propose that the voltage-gated opening of colicin E1 channels is accompanied by the insertion into the bilayer of a helical hairpin loop extending from residue 420 to residue 459, and that voltage-gated closing is associated with the extrusion of this loop from the interior of the bilayer back to the cis side.

scholarly journals Bilayer graphene oxide membranes for a wearable hemodialyzer

2020 ◽  
Author(s):  
Richard P. Rode ◽  
Henry H. Chung ◽  
Hayley N. Miller ◽  
Thomas R. Gaborski ◽  
Saeed Moghaddam
Keyword(s):  
Graphene Oxide ◽  
Cytochrome C ◽  
Self Assembly ◽  
Bilayer Membrane ◽  
Blood Proteins ◽  
High Mechanical Strength ◽  
Practical Applications ◽  
New Process ◽  
Improved Performance ◽  
Oxide Membranes

2D nanomaterials have long been considered for development of ultra-high throughput membranes, due to their atomically thin nature and high mechanical strength. However, current processes have yet to yield a viable membrane for practical applications due to the lack of scalability and substantially improved performance over existing membranes. Herein, a graphene oxide (GO) bilayer membrane with a permeability of 1562 mL/hr.mmHg.m2, two orders of magnitude higher than existing nanofiltration membranes, and a tight molecular weight cut-off (MWCO) is presented. To build such a membrane, we have developed a new process involving self-assembly and optimization of GO nanoplatelets physicochemical properties. The process produced a highly organized mosaic of nanoplatelets enabling ultra-high permeability and selectivity with only three layers of GO. Performance of the membrane has been evaluated in a simulated hemodialysis application, where it presents a great value proposition. The membrane has a precise molecular cut-off size of 5 nm, adjusted using a molecular interlinker, designed to prevent loss of critical blood proteins. Urea, cytochrome-c, and albumin are used as representative test molecules. Urea and cytochrome-c sieving coefficients of 0.5 and 0.4 were achieved under physiological pressure conditions, while retaining 99% of albumin. Hemolysis, complement activation, and coagulation studies exhibit a performance on par or superior to the existing hemodialyzer materials.

Reversal of mitochondrial swelling associated with fatty acid oxidation. II. Effects of cytochrome c and carnitine on contraction of fatty acid swollen mitochondria

1968 ◽  
Vol 46 (9) ◽  
pp. 1151-1160 ◽  
Author(s):  
Misako Nakatani ◽  
W. C. McMurray
Keyword(s):  
Fatty Acid ◽  
Cytochrome C ◽  
Energy Requirement ◽  
Liver Mitochondria ◽  
High Energy ◽  
Fatty Acyl ◽  
Water Soluble ◽  
Rat Liver Mitochondria ◽  
Acid Oxidation ◽  
Swelling Agent

Rat liver mitochondria undergo reversible swelling in the presence of a fatty acyl CoA generating system. Contraction of the swollen mitochondria was observed on the addition of either carnitine or cytochrome c. At low concentrations the two agents acted synergistically. At high concentrations cytochrome c completely replaced the requirement for carnitine.Cytochrome c also promoted the contraction of mitochondria swollen in the presence of fatty acid alone, provided that either ATP or ADP was added to initiate the contraction. The stimulation by cytochrome c was greater in the presence of ADP, and the contraction was more sensitive to respiratory inhibitors or dinitrophenol but was less sensitive to oligomycin than in the presence of ATP. Studies of the metabolism of 14C-labelled palmitate during cytochrome c induced contraction showed that decreases in mitochondrial-bound fatty acid and corresponding increases in water-soluble metabolites coincided with the reversal of swelling. The results indicated that the energy requirement for mitochondrial contraction in the presence of cytochrome c was provided by generation of high-energy intermediates coupled to oxidation of the fatty acid swelling agent.

scholarly journals Diffusion in phospholipid bilayer membranes: dual-leaflet dynamics and the roles of tracer–leaflet and inter-leaflet coupling

2014 ◽  
Vol 470 (2167) ◽  
pp. 20130843 ◽  
Author(s):  
Reghan J. Hill ◽  
Chih-Ying Wang
Keyword(s):  
Lateral Diffusion ◽  
Bilayer Membrane ◽  
Tracer Diffusion ◽  
Phospholipid Bilayer ◽  
Supported Membranes ◽  
Bilayer Membranes ◽  
Lubrication Film ◽  
Lipid Assemblies ◽  
Slip Coefficients ◽  
Made In

A variety of observations—sometimes controversial—have been made in recent decades when attempting to elucidate the roles of interfacial slip on tracer diffusion in phospholipid membranes. Evans–Sackmann theory (1988) has furnished membrane viscosities and lubrication-film thicknesses for supported membranes from experimentally measured lateral diffusion coefficients. Similar to the Saffman and Delbrück model, which is the well-known counterpart for freely supported membranes, the bilayer is modelled as a single two-dimensional fluid. However, the Evans–Sackman model cannot interpret the mobilities of monotopic tracers, such as individual lipids or rigidly bound lipid assemblies; neither does it account for tracer–leaflet and inter-leaflet slip. To address these limitations, we solve the model of Wang and Hill, in which two leaflets of a bilayer membrane, a circular tracer and supports are coupled by interfacial friction, using phenomenological friction/slip coefficients. This furnishes an exact solution that can be readily adopted to interpret the mobilities of a variety of mosaic elements—including lipids, integral monotopic and polytopic proteins, and lipid rafts—in supported bilayer membranes.

scholarly journals Chlorpromazine and carnitine-dependency of rat liver peroxisomal β-oxidation of long-chain fatty acids

1987 ◽  
Vol 241 (3) ◽  
pp. 783-791 ◽  
Author(s):  
J Vamecq
Keyword(s):  
Fatty Acids ◽  
Cytochrome C ◽  
Cytochrome C Oxidase ◽  
Rat Liver ◽  
Fatty Acyl ◽  
Carnitine Palmitoyltransferase ◽  
Acid Oxidation ◽  
Synthetase Activity ◽  
Mitochondrial Fatty Acid Oxidation ◽  
Mitochondrial Fatty Acid

The enzyme targets for chlorpromazine inhibition of rat liver peroxisomal and mitochondrial oxidations of fatty acids were studied. Effects of chlorpromazine on total fatty acyl-CoA synthetase activity, on both the first and the third steps of peroxisomal beta-oxidation, on the entry of fatty acyl-CoA esters into the peroxisome and on catalase activity, which allows breakdown of the H2O2 generated during the acyl-CoA oxidase step, were analysed. On all these metabolic processes, chlorpromazine was found to have no inhibitory action. Conversely, peroxisomal carnitine octanoyltransferase activity was depressed by 0.2-1 mM-chlorpromazine, which also inhibits mitochondrial carnitine palmitoyltransferase activity in all conditions in which these enzyme reactions are assayed. Different patterns of inhibition by the drug were, however, demonstrated for both these enzyme activities. Inhibitory effects of chlorpromazine on mitochondrial cytochrome c oxidase activity were also described. Inhibitions of both cytochrome c oxidase and carnitine palmitoyltransferase are proposed to explain the decreased mitochondrial fatty acid oxidation with 0.4-1.0 mM-chlorpromazine reported by Leighton, Persico & Necochea [(1984) Biochem. Biophys. Res. Commun. 120, 505-511], whereas depression by the drug of carnitine octanoyltransferase activity is presented as the factor responsible for the decreased peroxisomal beta-oxidizing activity described by the above workers.

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