Nitric oxide inhibits hypoxia‐induced impairment of human RBC deformability through reducing the cross‐linking of membrane protein band 3

Zhao, Yajin; Wang, Xiang; Wang, Ruofeng; Chen, Dong; Noviana, Milody; Zhu, Hongliang

doi:10.1002/jcb.27359

Cited by 8 publications

(8 citation statements)

References 71 publications

(155 reference statements)

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“…These biochemistry modifications were contributing to alterations on RBC deformability. NO may prevent these modifications ( 23 ). However, observations on RBC rheology from animal models must be interpreted with caution.…”

Section: Discussionmentioning

confidence: 99%

Effects of Preconditioning on RBC Deformability in Critically Ill Patients

Moreau

Boudjeltia

Biston

et al. 2022

Critical Care Explorations

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OBJECTIVES: RBCs from critically ill patients have depressed deformability, especially in sepsis. Prolonged exposure of RBCs from healthy volunteers to physiologic shear stress (the preconditioning technique) has been associated with improved deformability, but the effect of preconditioning on RBCs from critically ill patients with or without sepsis has never been studied. DESIGN: Prospective study. SETTING: A 32-bed medico-surgical ICU and a university-affiliated cell biology laboratory. SUBJECTS: RBCs from 26 healthy volunteers and 40 critically ill patients (20 with and 20 without sepsis). INTERVENTIONS: RBC deformability was measured using the elongation index (EI) with an ektacytometer, at shear stress levels ranging from 0.3 to 50 Pa. To assess the effects of preconditioning in the three groups, we measured EI after first applying a shear stress of 5 Pa for 300 seconds. To study the potential mechanisms involved in preconditioning, we looked at deformability after incubation of an RBC solution from the healthy volunteers with glutaraldehyde, a membrane-stabilizing protein, and neuraminidase, an enzyme that releases membrane sialic acid. MEASUREMENTS AND MAIN RESULTS: Baseline RBC deformability was significantly depressed in the septic patients compared with the volunteers at all shear stress levels greater than or equal to 4.89 Pa. Preconditioning improved deformability only in the volunteers (at shear stress levels of 0.48 and 0.76 Pa). Among the critically ill patients, preconditioning worsened RBC deformability at higher shear stress levels. After incubation (with glutaraldehyde or neuraminidase) of RBCs from five volunteers in whom preconditioning had significantly improved deformability, the positive effect of preconditioning was lost with glutaraldehyde. CONCLUSIONS: RBC deformability is depressed in septic patients. There was a deleterious effect of preconditioning on RBC deformability in septic patients, unlike the positive effect on RBCs from healthy volunteers. The effect of preconditioning may be associated with elasticity of the cell membrane.

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Section: Discussionmentioning

confidence: 99%

Effects of Preconditioning on RBC Deformability in Critically Ill Patients

Moreau

Boudjeltia

Biston

et al. 2022

Critical Care Explorations

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“…RBCs are permanently in danger of oxidative stress across their lifetime due to the high cellular concentration of oxygen and Hb [ 49 , 50 ]. It also leads to a series of changes, such as crosslinking of membrane protein, reduction of deformability, and release of MetHb, which further aggravates the free radical burst and causing secondary damage to the body [ 51 – 53 ]. In this study, we also found that oxidative stress induced membrane protein crosslinking and the presence of dysmorphic RBCs under in vitro oxidation conditions.…”

Section: Discussionmentioning

confidence: 99%

Downregulated Recycling Process but Not De Novo Synthesis of Glutathione Limits Antioxidant Capacity of Erythrocytes in Hypoxia

Wang

Zhao

Xiong

et al. 2020

Oxidative Medicine and Cellular Longevity

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Red blood cells (RBCs) are susceptible to sustained free radical damage during circulation, while the changes of antioxidant capacity and regulatory mechanism of RBCs under different oxygen gradients remain unclear. Here, we investigated the changes of oxidative damage and antioxidant capacity of RBCs in different oxygen gradients and identified the underlying mechanisms using an in vitro model of the hypoxanthine/xanthine oxidase (HX/XO) system. In the present study, we reported that the hypoxic RBCs showed much higher oxidative stress injury and lower antioxidant capacity compared with normoxic RBCs. In addition, we found that the disturbance of the recycling process, but not de novo synthesis of glutathione (GSH), accounted for the significantly decreased antioxidant capacity of hypoxic RBCs compared to normoxic RBCs. We further elucidated the underlying molecular mechanism by which oxidative phosphorylation of Band 3 blocked the hexose monophosphate pathway (HMP) and decreased NADPH production aggravating the dysfunction of GSH synthesis in hypoxic RBCs under oxidative conditions.

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“…The lipid composition in the RBC membrane including cholesterol, sphingomyelin and phosphatidylcholine is reduced in diabetes mellitus 2 patients (T2D) (2). It also suppresses tyrosine phosphorylation of band 3 phosphorylation under hypoxic conditions (51).…”

Section: Sem Analysis Of Stressed Rbcs and Recovery By 8 Bromo-cgmpmentioning

confidence: 99%

Nitric oxide donor 8-bromo-cGMP suppresses cholesterol depleted RBCs band 3 dysfunction

Vijayaraghavan¹,

Sengupta²,

Chatterjee³

et al. 2022

Cell Mol Biol (Noisy-le-grand)

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Red blood cells (RBCs) carry large cholesterol fractions and imbalance in them leads to several vascular complications. RBCs band 3 protein plays an important role in maintaining membrane integrity and there are many reports on cholesterol and band 3 protein interaction. Yet, RBCs band 3 protein role in regulating cholesterol homeostasis needs to be investigated. In this study, we induced cholesterol-depletion and band 3 inhibition in RBCs; both of which cause stress by decreasing band 3 channel activity with an increase in RBCs adhesion to endothelial cells (EC) by elevating band 3 phosphorylation (Tyr21), methemoglobin level and decreasing nitric oxide level. We hypothesized that nitric oxide (NO), a prominent determinant for RBC structural stability, would protect RBCs from stressors. To estimate this, we used three NO donors (SpNO, Sildenafil citrate and 8-Bromo-cGMP) and found that all 3 NO donors were able to recover, with 8-Bromo-cGMP being the most effective as it not only increased band 3 channel activity but also decreased RBC-EC adhesiveness and methemoglobin level in both stressors. Whereas NO donor's treatment did not display an ameliorative impact when both stresses were combined. Overall, these findings may shed light on the role of 8-bromo-cGMP in regulating RBC cholesterol homeostasis by maintaining band 3 function. Further studies in this direction might help identify targets for the therapeutic use of NO donors in the treatment of blood disorders.

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Nitric oxide inhibits hypoxia‐induced impairment of human RBC deformability through reducing the cross‐linking of membrane protein band 3

Abstract: NO may prevent decreased of RBCs deformability through reducing the cross-linking of membrane band 3 under hypoxia; this helps microvascular perfusion of RBCs during ischemic and hypoxic disease states.

Cited by 8 publications

References 71 publications

Effects of Preconditioning on RBC Deformability in Critically Ill Patients

Effects of Preconditioning on RBC Deformability in Critically Ill Patients

Downregulated Recycling Process but Not De Novo Synthesis of Glutathione Limits Antioxidant Capacity of Erythrocytes in Hypoxia

Nitric oxide donor 8-bromo-cGMP suppresses cholesterol depleted RBCs band 3 dysfunction

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