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

研究成果: Article査読

10 被引用数 (Scopus)


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.

ジャーナルAntioxidants and Redox Signaling
出版ステータスPublished - 2006 9月

ASJC Scopus subject areas

  • 生化学
  • 生理学
  • 分子生物学
  • 臨床生化学
  • 細胞生物学


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