From Experiments to Simulation: Shear-Induced Responses of Red Blood Cells to Different Oxygen Saturation Levels

Uğurel, Elif; Pişkin, Şenol; Aksu, Ali Cenk; Eser, Aysenur; Yalçın, Özlem

doi:10.3389/fphys.2019.01559

Cited by 12 publications

(5 citation statements)

References 82 publications

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“…On the contrary, it is recently indicated that gradually decreased O 2 pressure increases RBC deformability in a microfluidic channel (Wei et al, 2016). It is confirmed in another study that showed longer term (10 min) deoxygenation significantly increases shear‐induced RBC deformability (Ugurel et al, 2020). These findings demonstrated that RBCs regulate their mechanical properties in hypoxic conditions to pass easily through the capillaries under shear forces.…”

Section: Effect Of Oxygen Partial Pressure On Rbc Responsesmentioning

confidence: 55%

Section: Effect Of Oxygen Partial Pressure On Rbc Responsesmentioning

confidence: 77%

“…(a) Hb carrying oxygen and no interaction with membrane proteins in oxygenated state. (b) The association of Hb with membrane proteins while carrying no oxygen in deoxygenated state (Ugurel et al, 2020).…”

Section: Effect Of Oxygen Partial Pressure On Rbc Responsesmentioning

confidence: 99%

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Signaling mechanisms in red blood cells: A view through the protein phosphorylation and deformability

Cilek

Uğurel

Goksel

et al. 2023

Journal Cellular Physiology

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Intracellular signaling mechanisms in red blood cells (RBCs) involve various protein kinases and phosphatases and enable rapid adaptive responses to hypoxia, metabolic requirements, oxidative stress, or shear stress by regulating the physiological properties of the cell. Protein phosphorylation is a ubiquitous mechanism for intracellular signal transduction, volume regulation, and cytoskeletal organization in RBCs. Spectrin‐based cytoskeleton connects integral membrane proteins, band 3 and glycophorin C to junctional proteins, ankyrin and Protein 4.1. Phosphorylation leads to a conformational change in the protein structure, weakening the interactions between proteins in the cytoskeletal network that confers a more flexible nature for the RBC membrane. The structural organization of the membrane and the cytoskeleton determines RBC deformability that allows cells to change their ability to deform under shear stress to pass through narrow capillaries. The shear stress sensing mechanisms and oxygenation‐deoxygenation transitions regulate cell volume and mechanical properties of the membrane through the activation of ion transporters and specific phosphorylation events mediated by signal transduction. In this review, we summarize the roles of Protein kinase C, cAMP‐Protein kinase A, cGMP‐nitric oxide, RhoGTPase, and MAP/ERK pathways in the modulation of RBC deformability in both healthy and disease states. We emphasize that targeting signaling elements may be a therapeutic strategy for the treatment of hemoglobinopathies or channelopathies. We expect the present review will provide additional insights into RBC responses to shear stress and hypoxia via signaling mechanisms and shed light on the current and novel treatment options for pathophysiological conditions.

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Section: Effect Of Oxygen Partial Pressure On Rbc Responsesmentioning

confidence: 55%

Section: Effect Of Oxygen Partial Pressure On Rbc Responsesmentioning

confidence: 77%

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Signaling mechanisms in red blood cells: A view through the protein phosphorylation and deformability

Cilek

Uğurel

Goksel

et al. 2023

Journal Cellular Physiology

Self Cite

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“… 41 , 66 , 67 Recently, the deformability of erythrocytes was shown to be related to the duration of deoxygenation and the degree of hypoxia; it increased and then decreased with prolonged deoxygenation time in vitro. 68 Erythrocyte deformability was depressed in mildly hypoxia (12–16% O 2 ) but instead ascended in participants exposed to severe hypoxia (<10% O 2 ). 41 In patients with sickle cell anemia, hypoxia followed by reoxygenation significantly enhances the mechanical fragility of erythrocytes, leading to membrane damage.…”

Section: Hypoxia Affects Erythrocyte Membrane Propertiesmentioning

confidence: 96%

Metabolite and protein shifts in mature erythrocyte under hypoxia

Jin,

Zhang,

Wang

et al. 2024

iScience

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“…On the one hand, it increases the level of intracellular ATP, and, on the other hand, reduces the glucoses flux that enter the pentose phosphate pathway, which produces NADPH, necessary for the work of antioxidant enzymes, and reduced glutathione. Because CDB3 is the center of erythrocyte membrane organization and the regulator of ionic homeostasis, even minor changes in CDB3 binding lead to changes in the morpho-biochemical properties of cells (Ugurel et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Potential role of cytoplasmic protein binding to erythrocyte membrane in counteracting oxidative and metabolic stress

Dotsenko

Mykutska

Taradina

et al. 2020

Regul. Mech. Biosyst.

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The ability of protein to reversibly bind with membrane components is considered to be one of the oldest mechanisms of cell response to external stimuli. Erythrocytes have a well-developed mechanism of an adaptive response involving sorption-desorption processes, e.g. interactions of key glycolytic enzymes and hemoglobin with band 3 protein. A few publications have shown that under oxidative stress, cytoplasmic enzymes such as catalase, glutathione peroxidase and рeroxiredoxin bind to the erythrocyte membrane. The present work is a continuation of research in this direction to determine the causes and consequences of the interaction of cytoplasmic proteins with the membrane under conditions of oxidative stress and different glucose content. Human erythrocytes were incubated for five hours at 20 °C in an oxidizing medium of AscH – 1 · 10–4 M, Cu2+– 5 · 10–6 M with different glucose content (0–8 mM). Dynamic changes in the accumulation of membrane-bound hemoglobin, the distribution of ligand forms of hemoglobin in the cytoplasmic and membrane-bound fractions, the activity of membrane-associated and cytoplasmic forms of Cu/Zn superoxide dismutase (SOD1) and catalase, H2O2 content in extracellular and intracellular media were recorded. It was shown that binding of catalase and SOD1 to the erythrocyte membrane is initiated by oxidative stress and is a physiological function aimed at complete inactivation of extracellular and H2O2 and protection against their entry into the cell. It was shown that under conditions of glucose depletion and oxidative loading, catalase and SOD1 bind to the erythrocyte membrane, leading to inactivation of these enzymes. Membrane-bound hemoglobin was higher in cells incubated under these conditions than in glucose experiments. Glucose introduced into the incubation medium in an amount 4–8 mM causes complete binding of SOD1 to the membrane of erythrocytes, by involving it in the processes of casein kinase stabilization and glycolytic fluxes regulation. With mild oxidation, the amount of hemoglobin bound to the membrane does not change, indicating the presence of certain binding sites for hemoglobin with membrane proteins. We show that the activity of membrane-bound SOD1 along with the content of ligand forms in the composition of membrane-bound hemoglobin are informative indicators of the metabolic and redox state of erythrocytes.

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From Experiments to Simulation: Shear-Induced Responses of Red Blood Cells to Different Oxygen Saturation Levels

Cited by 12 publications

References 82 publications

Signaling mechanisms in red blood cells: A view through the protein phosphorylation and deformability

Signaling mechanisms in red blood cells: A view through the protein phosphorylation and deformability

Metabolite and protein shifts in mature erythrocyte under hypoxia

Potential role of cytoplasmic protein binding to erythrocyte membrane in counteracting oxidative and metabolic stress

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