Pros and cons of phospholipid asymmetry in erythrocytes

Sathi, Aiswarya; Viswanad, Vidya; Aneesh, T P; Kumar, Bala

doi:10.4103/0975-7406.129171

Cited by 17 publications

(5 citation statements)

References 19 publications

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“…To better understand the effect of the membrane-peptide interaction on the global CD spectra, reference measurements using the same titration were also performed with DOPC (dioleoyl-phosphatidylcholine) and DOPC/DOPG (dioleoyl-phosphatidylcholine/dioleyl-phosphatidylglycerol, 80/20 n/n%) liposomes, which can be considered as the simplest model system to mimic the outer leaflet of red blood cell membranes (Viswanad et al, 2014 ) ( Figures S1 , S2 ). When comparing the arithmetic sums of the individual CD curves of the free REV plus peptides ( Figure S3 ) as well as MAPs bound to liposomes ( Figure S1 ) it is obvious that the CD profile found for the REV plus MAP mixtures is distinct from such a simple combination of the two separate components.…”

Section: Resultsmentioning

confidence: 99%

Membrane Active Peptides Remove Surface Adsorbed Protein Corona From Extracellular Vesicles of Red Blood Cells

et al. 2020

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Besides the outstanding potential in biomedical applications, extracellular vesicles (EVs) are also promising candidates to expand our knowledge on interactions between vesicular surface proteins and small-molecules which exert biomembrane-related functions. Here we provide mechanistic details on interactions between membrane active peptides with antimicrobial effect (MAPs) and red blood cell derived EVs (REVs) and we demonstrate that they have the capacity to remove members of the protein corona from REVs even at lower than 5 µM concentrations. In case of REVs, the Soret-band arising from the membrane associated hemoglobins allowed to follow the detachment process by flow-Linear Dichroism (flow-LD). Further on, the significant change on the vesicle surfaces was confirmed by transmission electron microscopy (TEM). Since membrane active peptides, such as melittin have the affinity to disrupt vesicles, a combination of techniques, fluorescent antibody labeling, microfluidic resistive pulse sensing, and flow-LD were employed to distinguish between membrane destruction and surface protein detachment. The removal of protein corona members is a newly identified role for the investigated peptides, which indicates complexity of their in vivo function, but may also be exploited in synthetic and natural nanoparticle engineering. Furthermore, results also promote that EVs can be used as improved model systems for biophysical studies providing insight to areas with so far limited knowledge.

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Section: Resultsmentioning

confidence: 99%

Membrane Active Peptides Remove Surface Adsorbed Protein Corona From Extracellular Vesicles of Red Blood Cells

et al. 2020

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“…This normal disposition is known as phospholipid asymmetry. Lipid asymmetry is disturbed when the erythrocytes enter into eryptosis, and PS is exposed on RBCs surface [ 74 ]. This process involves three ATP and Ca 2+ -dependent transporters activation (flippase [ 75 ], floppase [ 76 ], and scramblase [ 77 ]).…”

Section: Discussionmentioning

confidence: 99%

Usnic Acid and Usnea barbata (L.) F.H. Wigg. Dry Extracts Promote Apoptosis and DNA Damage in Human Blood Cells through Enhancing ROS Levels

et al. 2021

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Nowadays, numerous biomedical studies performed on natural compounds and plant extracts aim to obtain highly selective pharmacological activities without unwanted toxic effects. In the big world of medicinal plants, Usnea barbata (L) F.H. Wigg (U. barbata) and usnic acid (UA) are well-known for their therapeutical properties. One of the most studied properties is their cytotoxicity on various tumor cells. This work aims to evaluate their cytotoxic potential on normal blood cells. Three dry U. barbata extracts in various solvents: ethyl acetate (UBEA), acetone (UBA), and ethanol (UBE) were prepared. From UBEA we isolated usnic acid with high purity by semipreparative chromatography. Then, UA, UBA, and UBE dissolved in 1% dimethyl sulfoxide (DMSO) and diluted in four concentrations were tested for their toxicity on human blood cells. The blood samples were collected from a healthy non-smoker donor; the obtained blood cell cultures were treated with the tested samples. After 24 h, the cytotoxic effect was analyzed through the mechanisms that can cause cell death: early and late apoptosis, caspase 3/7 activity, nuclear apoptosis, autophagy, reactive oxygen species (ROS) level and DNA damage. Generally, the cytotoxic effect was directly proportional to the increase of concentrations, usnic acid inducing the most significant response. At high concentrations, usnic acid and U. barbata extracts induced apoptosis and DNA damage in human blood cells, increasing ROS levels. Our study reveals the importance of prior natural products toxicity evaluation on normal cells to anticipate their limits and benefits as potential anticancer drugs.

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“…Plasma membrane asymmetry plays a critical role in the function of membrane proteins and in the interactions with the cytoskeleton, influencing the mechanical properties of the cell [ 39 ]. Asymmetric arrangement of plasma membrane phospholipids, especially the organization of phosphoinositides and PS to the inner leaflet, performs a key role in the integrity of the RBC [ 14 ]. By facilitating enzymatic reactions participating in membrane transport and signal transduction pathways, the phospholipid bilayer plays a key role in lipid homeostasis [ 5 ].…”

Section: Biochemical and Molecular Mechanisms Of Eryptosismentioning

confidence: 99%

“…Further, Ca 2+ influx also stimulates the formation of ceramide, which causes disruption of cell membrane asymmetry [ 12 , 13 ]. Plasma membrane asymmetry plays a critical role in the function of membrane proteins and in the interactions with the cytoskeleton, influencing the mechanical properties of the cell and performing a key role in the integrity of the RBC [ 14 ]. An increased number of erythrocytes with membrane dysfunction can lead to seriously detrimental health conditions, such as anemia, microcirculation dysfunction, and thrombogenic activation [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

Molecular Mechanisms and Pathophysiological Significance of Eryptosis

Alghareeb

Alfhili

Fatima

2023

IJMS

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Despite lacking the central apoptotic machinery, senescent or damaged RBCs can undergo an unusual apoptosis-like cell death, termed eryptosis. This premature death can be caused by, or a symptom of, a wide range of diseases. However, various adverse conditions, xenobiotics, and endogenous mediators have also been recognized as triggers and inhibitors of eryptosis. Eukaryotic RBCs are unique among their cell membrane distribution of phospholipids. The change in the RBC membrane composition of the outer leaflet occurs in a variety of diseases, including sickle cell disease, renal diseases, leukemia, Parkinson’s disease, and diabetes. Eryptotic erythrocytes exhibit various morphological alterations such as shrinkage, swelling, and increased granulation. Biochemical changes include cytosolic Ca2+ increase, oxidative stress, stimulation of caspases, metabolic exhaustion, and ceramide accumulation. Eryptosis is an effective mechanism for the elimination of dysfunctional erythrocytes due to senescence, infection, or injury to prevent hemolysis. Nevertheless, excessive eryptosis is associated with multiple pathologies, most notably anemia, abnormal microcirculation, and prothrombotic risk; all of which contribute to the pathogenesis of several diseases. In this review, we provide an overview of the molecular mechanisms, physiological and pathophysiological relevance of eryptosis, as well as the potential role of natural and synthetic compounds in modulating RBC survival and death.

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Pros and cons of phospholipid asymmetry in erythrocytes

Cited by 17 publications

References 19 publications

Membrane Active Peptides Remove Surface Adsorbed Protein Corona From Extracellular Vesicles of Red Blood Cells

Membrane Active Peptides Remove Surface Adsorbed Protein Corona From Extracellular Vesicles of Red Blood Cells

Usnic Acid and Usnea barbata (L.) F.H. Wigg. Dry Extracts Promote Apoptosis and DNA Damage in Human Blood Cells through Enhancing ROS Levels

Molecular Mechanisms and Pathophysiological Significance of Eryptosis

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