T-state stabilization of hemoglobin by nitric oxide to form α-nitrosyl heme causes constitutive release of ATP from human erythrocytes

Tomotaka Akatsu, Kosuke Tsukada, Takako Hishiki, Kazuhiro Suga-Numa, Minoru Tanabe, Motohide Shimazu, Yuko Kitagawa, Ayako Yachie-Kinoshita, Makoto Suematsu

Research output: Chapter in Book/Report/Conference proceedingConference contribution

6 Citations (Scopus)


Upon hypoxia, erythrocytes utilize hemoglobin (Hb) to trigger activation of glycolysis through its interaction with band 3. This process contributes to maintenance of ATP, a portion of which is released extracellularly to trigger endothelium-dependent vasorelaxation. However, whether the ATP release results either from metabolic activation of the cells secondarily or from direct regulation of the gating through Hb allostery remains unknown. This study aimed to examine if stabilization of T-state Hb could induce steadystate and hypoxia-induced alterations in glycolysis and the ATP release from erythrocytes. Treatment of deoxygenated erythrocytes with a nitric oxide (NO) donor generated a-NO Hb that is stabilized T-state allostery. Under these circumstances, the release of ATP was significantly elevated even under normoxia and not further enhanced upon hypoxia. These events did not coincide with activation of glycolysis of the cells, so far as judged by the fact that intracellular ATP was significantly decreased by the NO treatment. Collectively, the present study suggests that hypoxia-induced ATP release is triggered through mechanisms involving R-T transition of Hb, and the gating process might occur irrespective of hypoxia-responsive regulation of glycolysis.

Original languageEnglish
Title of host publicationOxygen Transport to Tissue XXXI
EditorsEiji Takahashi, Duane Bruley
Number of pages6
Publication statusPublished - 2010 Dec 1

Publication series

NameAdvances in Experimental Medicine and Biology
ISSN (Print)0065-2598

ASJC Scopus subject areas

  • General Biochemistry,Genetics and Molecular Biology


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