Acetylsalicylic acid (aspirin) and salicylic acid interaction with the human erythrocyte membrane bilayer induce in vitro changes in the morphology of erythrocytes

Suwalsky, Mario; Belmar, Jessica; Villena, Fernando Pardo-Manuel de; Gallardo, María José; Jemioła-Rzemińska, Małgorzata; Strzałka, Kazimierz

doi:10.1016/j.abb.2013.09.006

Cited by 39 publications

(19 citation statements)

References 42 publications

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“…n-Butyric acid changes the fluidity of the cell membrane of colon cancer cells [18], while salicylic acid derivatives, which are also derivatives of benzoic acid, affect the plasma membrane and change the shape, stiffness and relaxation time of isolated RBCs [19]. Based on X-ray diffraction and fluorescence spectroscopy studies, it has recently been reported that acetylsalicylic acid and salicylic acid interact with human erythrocytes and perturb the membrane bilayer [20]. These results suggest that both the carboxylic acids investigated in this study might also change the Based on the same experimental techniques as those used in the present study, we previously reported, that some monocarboxylic acids increase OF, whereas their corresponding dicarboxylic acids decrease OF in rat RBCs [11].…”

Section: Discussionmentioning

confidence: 99%

Monocarboxylic Acids and Dicarboxylic Acids Induce Different Responses in terms of Osmotic Fragility in Rat and Guinea Pig Erythrocytes In vitro

Mineo¹,

Kasai²,

Makihara³

et al. 2016

J Membra Sci Technol

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We compared the effects of monocarboxylic and dicarboxylic acids on osmotic fragility (OF) in rat and guinea pig red blood cells (RBCs) in vitro. Monocarboxylic acids possessing 4 to 8 straight-chain hydrocarbons increased OF in rat RBCs in a concentration-dependent manner. The increases in OF were also dependent on the number of carbons in the hydrocarbon chain bonded to the carboxylic group. Benzoic and cyclohexane-monocarboxylic acids also increased OF in rat RBCs in a dose-dependent manner. Although most of the dicarboxylic acids possessing a straight hydrocarbon chain decreased OF in rat RBCs, malonic acid showed the greatest potential to decrease OF among the substances tested. None of the monocarboxylic acids increased OF in guinea pig RBCs. Among the dicarboxylic acids possessing a benzene ring, isophthalic and terephthalic, but not phthalic acid, decreased OF in rat RBCs dose-dependently. Three cyclohexane-dicarboxylic acids decreased OF in guinea pig RBCs, while they had no effect on OF in rat RBCs. With regard to the action of those carboxylic acids on the cell membrane, hydrophobic hydrocarbons of a certain structure are thought to enter the phospholipid layer with the hydrophilic carboxylic group remaining at the membrane surface where it affects the nature of the cell membrane, thus changing osmotic resistance in the RBCs. Inter-species differences in the RBC membrane were confirmed in the OF response to those carboxylic acids. The differences in OF response to the monocarboxylic and dicarboxylic acids observed in rat and guinea pig RBCs are speculated to be due to differences in the nature of the RBC membrane formed by the various phospholipids.

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Section: Discussionmentioning

confidence: 99%

Monocarboxylic Acids and Dicarboxylic Acids Induce Different Responses in terms of Osmotic Fragility in Rat and Guinea Pig Erythrocytes In vitro

Mineo¹,

Kasai²,

Makihara³

et al. 2016

J Membra Sci Technol

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“…[72][73][74] Aspirin has been shown to have a high affinity for phospholipids, 47 and to perturb lipid bilayers in a concentration dependent manner. 75 Suwalsky et al 75 found that ASA strongly perturbed model membranes made of DMPC and DMPE, predominantly found in the outer and inner monolayers of the human erythrocyte membrane and observed that aspirin affects the human erythrocyte shape. In addition, non-steroidal anti-inammatory drugs such as aspirin and ibuprofen have been shown to increase membrane uidity and the incidence of pores, decrease the hydrophobic surface barrier, leading to diffusion of acid and cellular injury.…”

Section: Effect Of Aspirinmentioning

confidence: 99%

“…Membranes containing ASA were previously studied using X-ray diffraction. 46,75,81 While cholesterol is known to reside in the hydrophobic membrane core and to align parallel to the saturated lipid tails (see, e.g., ref. 8 and 67), in agreement with the umbrella model, ASA is located among the head groups of the lipid molecules.…”

Section: The Interaction Of Aspirin With Membranesmentioning

confidence: 99%

Acetylsalicylic acid (ASA) increases the solubility of cholesterol when incorporated in lipid membranes

et al. 2014

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Cholesterol has been well established as a mediator of cell membrane fluidity. By interacting with lipid tails, cholesterol causes the membrane tails to be constrained thereby reducing membrane fluidity, well known as the condensation effect. Acetylsalicylic acid (ASA), the main ingredient in aspirin, has recently been shown to increase fluidity in lipid bilayers by primarily interacting with lipid head groups. We used high-resolution X-ray diffraction to study both ASA and cholesterol coexisting in model membranes of dimyristoylphosphatidylcholine (DMPC). While a high cholesterol concentration of 40 mol% cholesterol leads to the formation of immiscible cholesterol bilayers, as was reported previously, increasing the amount of ASA in the membranes between 0 to 12.5 mol% was found to significantly increase the fluidity of the bilayers and dissolve the cholesterol plaques. We, therefore, present experimental evidence for an interaction between cholesterol and ASA on the level of the cell membrane at elevated levels of cholesterol and ASA.

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“…Aspirin is the most common NSAID and is known to interact with membranes 15,68 . Aspirin strongly perturbs model membrane structure in a concentration dependent manner and also influences human erythrocyte shape 70 . It decreases the hydrophobic surface barrier in mucosal membranes, leading to a diffusion of acid and gastrointestinal injury 71 and impacts on protein sorting 72 .…”

Section: Discussionmentioning

confidence: 99%

The Molecular Structure of Human Red Blood Cell Membranes From Highly Oriented, Solid Supported Multi-Lamellar Membranes

Himbert

Alsop

Rheinstädter

2018

Biophysical Journal

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We prepared highly oriented, multi-lamellar stacks of human red blood cell (RBC) membranes applied on silicon wafers. RBC ghosts were prepared by hemolysis and applied onto functionalized silicon chips and annealed into multi-lamellar RBC membranes. High resolution X-ray diffraction was used to determine the molecular structure of the stacked membranes. We present direct experimental evidence that these RBC membranes consist of nanometer sized domains of integral coiled-coil peptides, as well as liquid ordered (l o ) and liquid disordered (l d ) lipids. Lamellar spacings, membrane and hydration water layer thicknesses, areas per lipid tail and domain sizes were determined. The common drug aspirin was added to the RBC membranes and found to interact with RBC membranes and preferably partition in the head group region of the l o domain leading to a fluidification of the membranes, i.e., a thinning of the bilayers and an increase in lipid tail spacing. Our results further support current models of RBC membranes as patchy structures and provide unprecedented structural details of the molecular organization in the different domains.The presence of pale cells with no internal content in a blood smear is typically indicative of a disease. These cells are produced by hemolysis and have been named red blood cell (RBC) ghosts based on their appearance under the microscope. RBC ghosts can be prepared artificially [1][2][3] . The first published protocol in 1963 by Dodge, Mitchell and Hanahan describes the extraction of the cell membrane from RBCs through hemolysis and was an essential step in the development of membrane proteomics and lipidomics 4,5 . While there is detailed knowledge of the composition of RBC membranes, information about the molecular organization of these components in the actual membranes is scarce 6 . This is, in particular, a consequence of the lack of suitable experimental techniques. The disordered, patchy and highly dynamic state of biological materials impedes, for instance, the use of high-resolution diffraction techniques as in protein crystallography. To overcome this constraint, we prepared highly oriented stacks of RBC membranes on silicon wafers and studied their molecular properties in-vitro using high resolution X-ray diffraction. The results present evidence for nanometer-sized domains of coiled-coils peptides, as well as liquid ordered (l o ) and liquid disordered (l d ) lipid patches, and give a detailed picture of the molecular organization in these domains.When present in the body, aspirin (acetylsalicylic acid, ASA) and its metabolites interact with the cyclo-oxygenase (COX) pathway. The inhibition of both COX isoforms, COX-1 and COX-2, by higher dose aspirin is believed to lead to analgesic and anti-inflammatory effects, while lower doses, sufficient to inhibit COX-1 activity, lead to anti-platelet activity 7,8 . There is recent evidence that membrane composition and fluidity play an important role in platelet cell function [9][10][11] , possibly related to the formation of rafts 12 .

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Acetylsalicylic acid (aspirin) and salicylic acid interaction with the human erythrocyte membrane bilayer induce in vitro changes in the morphology of erythrocytes

Cited by 39 publications

References 42 publications

Monocarboxylic Acids and Dicarboxylic Acids Induce Different Responses in terms of Osmotic Fragility in Rat and Guinea Pig Erythrocytes In vitro

Monocarboxylic Acids and Dicarboxylic Acids Induce Different Responses in terms of Osmotic Fragility in Rat and Guinea Pig Erythrocytes In vitro

Acetylsalicylic acid (ASA) increases the solubility of cholesterol when incorporated in lipid membranes

The Molecular Structure of Human Red Blood Cell Membranes From Highly Oriented, Solid Supported Multi-Lamellar Membranes

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