Hydrogen Sulfide Is a Regulator of Hemoglobin Oxygen-Carrying Capacity via Controlling 2,3-BPG Production in Erythrocytes

Copyright © 2021 Gang Wang et al..

Hydrogen sulfide (H2S) is naturally synthesized in a wide range of mammalian tissues. Whether H2S is involved in the regulation of erythrocyte functions remains unknown. Using mice with a genetic deficiency in a H2S natural synthesis enzyme cystathionine-γ-lyase (CSE) and high-throughput metabolomic profiling, we found that levels of erythrocyte 2,3-bisphosphoglycerate (2,3-BPG), an erythroid-specific metabolite negatively regulating hemoglobin- (Hb-) oxygen (O2) binding affinity, were increased in CSE knockout (Cse -/-) mice under normoxia. Consistently, the 50% oxygen saturation (P50) value was increased in erythrocytes of Cse -/- mice. These effects were reversed by treatment with H2S donor GYY4137. In the models of cultured mouse and human erythrocytes, we found that H2S directly acts on erythrocytes to decrease 2,3-BPG production, thereby enhancing Hb-O2 binding affinity. Mouse genetic studies showed that H2S produced by peripheral tissues has a tonic inhibitory effect on 2,3-BPG production and consequently maintains Hb-O2 binding affinity in erythrocytes. We further revealed that H2S promotes Hb release from the membrane to the cytosol and consequently enhances bisphosphoglycerate mutase (BPGM) anchoring to the membrane. These processes might be associated with S-sulfhydration of Hb. Moreover, hypoxia decreased the circulatory H2S level and increased the erythrocyte 2,3-BPG content in mice, which could be reversed by GYY4137 treatment. Altogether, our study revealed a novel signaling pathway that regulates oxygen-carrying capacity in erythrocytes and highlights a previously unrecognized role of H2S in erythrocyte 2,3-BPG production.

Medienart:

E-Artikel

Erscheinungsjahr:

2021

Erschienen:

2021

Enthalten in:

Zur Gesamtaufnahme - volume:2021

Enthalten in:

Oxidative medicine and cellular longevity - 2021(2021) vom: 24., Seite 8877691

Sprache:

Englisch

Beteiligte Personen:

Wang, Gang [VerfasserIn]
Huang, Yan [VerfasserIn]
Zhang, Ningning [VerfasserIn]
Liu, Wenhu [VerfasserIn]
Wang, Changnan [VerfasserIn]
Zhu, Xiaoyan [VerfasserIn]
Ni, Xin [VerfasserIn]

Links:

Volltext

Themen:

138-81-8
2,3-Diphosphoglycerate
Bisphosphoglycerate Mutase
EC 5.4.2.4
Hemoglobins
Hydrogen Sulfide
Journal Article
Oxygen
S88TT14065
Sulfates
YY9FVM7NSN

Anmerkungen:

Date Completed 09.09.2021

Date Revised 26.02.2024

published: Electronic-eCollection

Citation Status MEDLINE

doi:

10.1155/2021/8877691

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM32186669X