Erythrocytes enhance oxygen-carrying capacity through self-regulation

Once considered passive carriers of oxygen, erythrocytes are now understood to play active roles in regulating oxygen homeostasis and redox balance. This review examines the molecular mechanisms through which red blood cells adapt to hypoxic conditions, including nitric oxide (NO)-driven changes in...

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Main Authors: Ying Xu, Zhangjie Yu, Hanxuan Liu, Xiaohan Bian, Weiliang Tang
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-05-01
Series:Frontiers in Physiology
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Online Access:https://www.frontiersin.org/articles/10.3389/fphys.2025.1592176/full
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author Ying Xu
Zhangjie Yu
Hanxuan Liu
Xiaohan Bian
Weiliang Tang
author_facet Ying Xu
Zhangjie Yu
Hanxuan Liu
Xiaohan Bian
Weiliang Tang
author_sort Ying Xu
collection DOAJ
description Once considered passive carriers of oxygen, erythrocytes are now understood to play active roles in regulating oxygen homeostasis and redox balance. This review examines the molecular mechanisms through which red blood cells adapt to hypoxic conditions, including nitric oxide (NO)-driven changes in membrane properties, βCys93-dependent S-nitrosylation, adenosine-induced activation of glycolysis, and the development of hypoxic memory via eENT1 degradation. Enzymes such as RBC eNOS, CYB5R3, and G6PD are essential for maintaining NO availability and redox balance by controlling redox state and NADPH synthesis. In addition to their role in gas transport, erythrocytes contribute to intercellular communication, retain organelle remnants under pathological conditions, and are being explored as platforms for drug delivery. Progress in nanotechnology and gene editing has expanded their clinical applications. These findings present erythrocytes as adaptable, multifunctional cells that connect cellular metabolism, vascular biology, and translational research.
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institution OA Journals
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language English
publishDate 2025-05-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Physiology
spelling doaj-art-227a63c93fe6414d8d4f2432c94a8dbc2025-08-20T01:51:44ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2025-05-011610.3389/fphys.2025.15921761592176Erythrocytes enhance oxygen-carrying capacity through self-regulationYing Xu0Zhangjie Yu1Hanxuan Liu2Xiaohan Bian3Weiliang Tang4School of Medicine, ShaoXing University, Shaoxing, Zhejiang Province, ChinaDepartment of Cardiology, Shaoxing People's Hospital, Shaoxing, Zhejiang, ChinaDepartment of Cardiology, Shaoxing People's Hospital, Shaoxing, Zhejiang, ChinaSchool of Medicine, ShaoXing University, Shaoxing, Zhejiang Province, ChinaSchool of Medicine, ShaoXing University, Shaoxing, Zhejiang Province, ChinaOnce considered passive carriers of oxygen, erythrocytes are now understood to play active roles in regulating oxygen homeostasis and redox balance. This review examines the molecular mechanisms through which red blood cells adapt to hypoxic conditions, including nitric oxide (NO)-driven changes in membrane properties, βCys93-dependent S-nitrosylation, adenosine-induced activation of glycolysis, and the development of hypoxic memory via eENT1 degradation. Enzymes such as RBC eNOS, CYB5R3, and G6PD are essential for maintaining NO availability and redox balance by controlling redox state and NADPH synthesis. In addition to their role in gas transport, erythrocytes contribute to intercellular communication, retain organelle remnants under pathological conditions, and are being explored as platforms for drug delivery. Progress in nanotechnology and gene editing has expanded their clinical applications. These findings present erythrocytes as adaptable, multifunctional cells that connect cellular metabolism, vascular biology, and translational research.https://www.frontiersin.org/articles/10.3389/fphys.2025.1592176/fullerythrocyteshypoxianitric oxideadenosineβCys93drug delivery systems
spellingShingle Ying Xu
Zhangjie Yu
Hanxuan Liu
Xiaohan Bian
Weiliang Tang
Erythrocytes enhance oxygen-carrying capacity through self-regulation
Frontiers in Physiology
erythrocytes
hypoxia
nitric oxide
adenosine
βCys93
drug delivery systems
title Erythrocytes enhance oxygen-carrying capacity through self-regulation
title_full Erythrocytes enhance oxygen-carrying capacity through self-regulation
title_fullStr Erythrocytes enhance oxygen-carrying capacity through self-regulation
title_full_unstemmed Erythrocytes enhance oxygen-carrying capacity through self-regulation
title_short Erythrocytes enhance oxygen-carrying capacity through self-regulation
title_sort erythrocytes enhance oxygen carrying capacity through self regulation
topic erythrocytes
hypoxia
nitric oxide
adenosine
βCys93
drug delivery systems
url https://www.frontiersin.org/articles/10.3389/fphys.2025.1592176/full
work_keys_str_mv AT yingxu erythrocytesenhanceoxygencarryingcapacitythroughselfregulation
AT zhangjieyu erythrocytesenhanceoxygencarryingcapacitythroughselfregulation
AT hanxuanliu erythrocytesenhanceoxygencarryingcapacitythroughselfregulation
AT xiaohanbian erythrocytesenhanceoxygencarryingcapacitythroughselfregulation
AT weiliangtang erythrocytesenhanceoxygencarryingcapacitythroughselfregulation