Erythrocytes with T-state-stabilized hemoglobin as a therapeutic tool for postischemic liver dysfunction

Kazuhiro Suganuma, Kosuke Tsukada, Misato Kashiba, Antonio Tsuneshige, Toshiharu Furukawa, Tetsuro Kubota, Nobuhito Goda, Masaki Kitajima, Takashi Yonetani, Makoto Suematsu

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

This study aimed to examine if T-state stabilization of hemoglobin in erythrocytes could protect against postischemic organ injury. Human erythrocytes containing three different states of Hb allostery were prepared: control Hb (hRBC), CO-Hb that is stabilized under R-state with the 6-coodinated prosthetic heme (CO-hRBC), and α-NO-deoxyHb stabilized under T-state (α-NO-hRBC). To prepare α-NO-RBC, deoxygenated RBC was treated with FK409, a thiol-free NO donor, at its half molar concentration to that of Hb; this procedure resulted in the 5-coordinated NO binding on the α-subunit heme, as judged by electron spin resonance spectrometry. Rats were subject to 20 min systemic hemorrhage to maintain mean arterial pressure at 40 mm Hg, and reperfused with one of hRBCs. This protocol for ischemia, followed by 60 min reperfusion with physiological saline, caused modest metabolic acidosis and cholestasis. Administration of hRBC or CO-hRBC significantly attenuated cholestasis and improved acidosis. Rats treated with α-NO-hRBC exhibited greater recovery of metabolic acidosis and bile excretion than those treated with hRBC or CO-hRBC, displaying the best outcome of local oxygen utilization in hepatic lobules. Half-life time of α-NO-RBC administered in vivo was approximately 60 min. These results suggest that T-state Hb stabilization by NO serves as a stratagem to treat postischemic organ dysfunction.

Original languageEnglish
Pages (from-to)1847-1855
Number of pages9
JournalAntioxidants and Redox Signaling
Volume8
Issue number9-10
DOIs
Publication statusPublished - 2006 Sep
Externally publishedYes

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Carbon Monoxide
Liver
Liver Diseases
Hemoglobins
Acidosis
Erythrocytes
Cholestasis
Heme
Rats
Stabilization
Electron Spin Resonance Spectroscopy
Therapeutics
Prosthetics
Sulfhydryl Compounds
Bile
Spectrometry
Reperfusion
Paramagnetic resonance
Half-Life
Spectrum Analysis

ASJC Scopus subject areas

  • Biochemistry

Cite this

Suganuma, K., Tsukada, K., Kashiba, M., Tsuneshige, A., Furukawa, T., Kubota, T., ... Suematsu, M. (2006). Erythrocytes with T-state-stabilized hemoglobin as a therapeutic tool for postischemic liver dysfunction. Antioxidants and Redox Signaling, 8(9-10), 1847-1855. https://doi.org/10.1089/ars.2006.8.1847

Erythrocytes with T-state-stabilized hemoglobin as a therapeutic tool for postischemic liver dysfunction. / Suganuma, Kazuhiro; Tsukada, Kosuke; Kashiba, Misato; Tsuneshige, Antonio; Furukawa, Toshiharu; Kubota, Tetsuro; Goda, Nobuhito; Kitajima, Masaki; Yonetani, Takashi; Suematsu, Makoto.

In: Antioxidants and Redox Signaling, Vol. 8, No. 9-10, 09.2006, p. 1847-1855.

Research output: Contribution to journalArticle

Suganuma, K, Tsukada, K, Kashiba, M, Tsuneshige, A, Furukawa, T, Kubota, T, Goda, N, Kitajima, M, Yonetani, T & Suematsu, M 2006, 'Erythrocytes with T-state-stabilized hemoglobin as a therapeutic tool for postischemic liver dysfunction', Antioxidants and Redox Signaling, vol. 8, no. 9-10, pp. 1847-1855. https://doi.org/10.1089/ars.2006.8.1847
Suganuma, Kazuhiro ; Tsukada, Kosuke ; Kashiba, Misato ; Tsuneshige, Antonio ; Furukawa, Toshiharu ; Kubota, Tetsuro ; Goda, Nobuhito ; Kitajima, Masaki ; Yonetani, Takashi ; Suematsu, Makoto. / Erythrocytes with T-state-stabilized hemoglobin as a therapeutic tool for postischemic liver dysfunction. In: Antioxidants and Redox Signaling. 2006 ; Vol. 8, No. 9-10. pp. 1847-1855.
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