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Modulation of the Oxygenation State and Intracellular pH of Erythrocytes by Inositol‐Trispyrophosphate Investigated by 31P NMR Study of 2,3‐DPG
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Modulation of the Oxygenation State and Intracellular pH of Erythrocytes by Inositol‐Trispyrophosphate Investigated by 31P NMR Study of 2,3‐DPG
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Modulation of the Oxygenation State and Intracellular pH of Erythrocytes by Inositol‐Trispyrophosphate Investigated by 31P NMR Study of 2,3‐DPG
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Journal Article
Modulation of the Oxygenation State and Intracellular pH of Erythrocytes by Inositol‐Trispyrophosphate Investigated by 31P NMR Study of 2,3‐DPG
2025
Overview
The hypoxic microenvironment is crucial for tumour cell growth and invasiveness. Tumour tissue results from adaptation to reduced oxygen availability. Hypoxia first activates pro‐angiogenic signals for alleviation. Pathologic, tumour angiogenesis maintains hypoxia, impairing treatment outcomes. Vessel normalisation requires physioxia. Oxygen delivery by red blood cell (RBC) carrying haemoglobin (Hb) is enhanced by myo‐inositol trispyrophosphate (ITPP), an effector of oxygen transport by RBCs. Altering glycolytic activity, it lowers intracellular pH and increases oxygen release from Hb. 31P NMR tracking of 2,3‐diphosphoglycerate (2,3‐DPG), allosteric effector of Hb and non‐penetrating anion in RBCs, reports on erythrocytes internal environment. 31P resonances of 2,3‐DPG are pH‐sensitive, their positions indicate the oxygenation state of RBCs and interactions with effectors such as ITPP. Here we show in vitro and in vivo, that modifying Hb activity through band‐3 anion transporter, ITPP enhances oxygen release and controls RBC internal pH. Its blood availability validates applicability of ITPP‐based strategies.
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