Effects of Hypoxia on Erythrocyte Membrane Properties—Implications for Intravascular Hemolysis and Purinergic Control of Blood Flow

Grygorczyk, Ryszard; Orlov, Sergei N.

doi:10.3389/fphys.2017.01110

Cited by 54 publications

(35 citation statements)

References 97 publications

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“…As stated by Dr. Grygorczyk’s group 4 , 36 , in vitro haemolysis of RBCs can significantly contribute to elevation of [ATPe], depending on the experimental conditions. Thus, when analysing ATP release from RBCs, haemolysis has to be assessed to distinguish lytic from non-lytic (regulated) mechanisms of ATP release.…”

Section: Resultsmentioning

confidence: 99%

Human erythrocytes release ATP by a novel pathway involving VDAC oligomerization independent of pannexin-1

Marginedas-Freixa

Álvarez

Moras

et al. 2018

Sci Rep

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We previously demonstrated that the translocase protein TSPO2 together with the voltage-dependent anion channel (VDAC) and adenine nucleotide transporter (ANT) were involved in a membrane transport complex in human red blood cells (RBCs). Because VDAC was proposed as a channel mediating ATP release in RBCs, we used TSPO ligands together with VDAC and ANT inhibitors to test this hypothesis. ATP release was activated by TSPO ligands, and blocked by inhibitors of VDAC and ANT, while it was insensitive to pannexin-1 blockers. TSPO ligand increased extracellular ATP (ATPe) concentration by 24–59% over the basal values, displaying an acute increase in [ATPe] to a maximal value, which remained constant thereafter. ATPe kinetics were compatible with VDAC mediating a fast but transient ATP efflux. ATP release was strongly inhibited by PKC and PKA inhibitors as well as by depleting intracellular cAMP or extracellular Ca2+, suggesting a mechanism involving protein kinases. TSPO ligands favoured VDAC polymerization yielding significantly higher densities of oligomeric bands than in unstimulated cells. Polymerization was partially inhibited by decreasing Ca2+ and cAMP contents. The present results show that TSPO ligands induce polymerization of VDAC, coupled to activation of ATP release by a supramolecular complex involving VDAC, TSPO2 and ANT.

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Section: Resultsmentioning

confidence: 99%

Human erythrocytes release ATP by a novel pathway involving VDAC oligomerization independent of pannexin-1

Marginedas-Freixa

Álvarez

Moras

et al. 2018

Sci Rep

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“…Thus, the decrease in deoxygenation-induced ATP release from RBCs following incubation with diamide in Study 1 is likely to be due primarily to the decrease in RBC deformability. It has been suggested recently that RBC ATP release occurs primarily through haemolysis rather than a regulated export process (Sikora et al 2014;Grygorczyk & Orlov, 2017). However, while haemolysis can certainly contribute to ATP release and is an important methodological challenge that must be controlled for in studies such as these (Keller et al 2017), the collective experimental evidence does not support the hypothesis that haemolysis is a primary mechanism for ATP release from human RBCs (Kirby et al 2015).…”

Section: Experimental Considerations and Limitationsmentioning

confidence: 99%

Reduced deformability contributes to impaired deoxygenation‐induced ATP release from red blood cells of older adult humans

Racine

Dinenno

2019

The Journal of Physiology

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Red blood cells (RBCs) release ATP in response to deoxygenation, which can increase blood flow to help match oxygen supply with tissue metabolic demand. r This release of ATP is impaired in RBCs from older adults, but the underlying mechanisms are unknown. r In this study, improving RBC deformability in older adults restored deoxygenation-induced ATP release, whereas decreasing RBC deformability in young adults reduced ATP release to the level of that of older adults. r In contrast, treating RBCs with a phosphodiesterase 3 inhibitor did not affect ATP release in either age group, possibly due to intact intracellular signalling downstream of deoxygenation as indicated by preserved cAMP and ATP release responses to pharmacological G i protein activation in RBCs from older adults. r These findings are the first to demonstrate that the age-related decrease in RBC deformability is a primary mechanism of impaired deoxygenation-induced ATP release, which may have implications for treating impaired vascular control with advancing age.

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“…Mechanical stress may lead to the complete destruction of the RBC. Depending on how big the stress is, how long it acts, and what the RBC condition is, hemolysis may occur immediately or with delay ( Kameneva et al, 2004 ; Cabrales, 2007 ; Grygorczyk and Orlov, 2017 ). Non-physiological flow conditions cause a decrease in RBC deformability and membrane potential, promoting a high blood viscosity.…”

Section: Introductionmentioning

confidence: 99%

Low-Level Light Therapy Protects Red Blood Cells Against Oxidative Stress and Hemolysis During Extracorporeal Circulation

et al. 2018

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Aim: An activation of non-specific inflammatory response, coagulation disorder, and blood morphotic elements damage are the main side effects of the extracorporeal circulation (ECC). Red-to-near-infrared radiation (R/NIR) is thought to be capable of stabilizing red blood cell (RBC) membrane through increasing its resistance to destructive factors. We focused on the development of a method using low-level light therapy (LLLT) in the spectral range of R/NIR which could reduce blood trauma caused by the heart-lung machine during surgery.Methods: R/NIR emitter was adjusted in terms of geometry and optics to ECC circuit. The method of extracorporeal blood photobiomodulation was tested during in vivo experiments in an animal, porcine model (1 h of ECC plus 23 h of animal observation). A total of 24 sows weighing 90–100 kg were divided into two equal groups: control one and LLLT. Blood samples were taken during the experiment to determine changes in blood morphology [RBC and white blood cell (WBC) counts, hemoglobin (Hgb)], indicators of hemolysis [plasma-free hemoglobin (PFHgb), serum bilirubin concentration, serum lactate dehydrogenase (LDH) activity], and oxidative stress markers [thiobarbituric acid reactive substances (TBARS) concentration, total antioxidant capacity (TAC)].Results: In the control group, a rapid systemic decrease in WBC count during ECC was accompanied by a significant increase in RBC membrane lipids peroxidation, while in the LLLT group the number of WBC and TBARS concentration both remained relatively constant, indicating limitation of the inflammatory process. These results were consistent with the change in the hemolysis markers like PFHgb, LDH, and serum bilirubin concentration, which were significantly reduced in LLLT group. No differences in TAC, RBC count, and Hgb concentration were detected.Conclusion: We presented the applicability of the LLLT with R/NIR radiation to blood trauma reduction during ECC.

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Effects of Hypoxia on Erythrocyte Membrane Properties—Implications for Intravascular Hemolysis and Purinergic Control of Blood Flow

Cited by 54 publications

References 97 publications

Human erythrocytes release ATP by a novel pathway involving VDAC oligomerization independent of pannexin-1

Human erythrocytes release ATP by a novel pathway involving VDAC oligomerization independent of pannexin-1

Reduced deformability contributes to impaired deoxygenation‐induced ATP release from red blood cells of older adult humans

Low-Level Light Therapy Protects Red Blood Cells Against Oxidative Stress and Hemolysis During Extracorporeal Circulation

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