title: Preparation and characterization of SNO-PEG-hemoglobin as a candidate for oxygen transporting material.
abstract: Acellular hemoglobin (Hb) derivates developed as oxygen carriers are known to cause hypertensive reactions due to their nitric oxide (NO) scavenging action. To modulate this undesired activity, we have developed a new Hb derivative, s-nitrosylated polyethylene glycol (PEG)-modified hemoglobin (SNO-PEG-Hb), which can deliver oxygen and NO. After human Hb was modified with PEG to increase its molecular weight, the free sulfhydryl groups of Hb were s-nitrosylated with s-nitrosoglutathione. Administration of unmodified Hb into anesthetized rats caused a hypertensive reaction, while s-nitrosylated Hb derivatives such as SNO-Hb and SNO-PEG-Hb did not raise blood pressure. The plasma half-lives of heme and NO bound to SNO-PEG-Hb were 11.5 and 2.4 hours respectively, indicating that the s-nitrosylated Hb derivative may act as a slow-releasing agent for NO. Based on these findings, SNO-PEG-Hb is a useful candidate for a blood substitute and tool for oxygen therapeutics.
authors: Tohoku University School of Medicine, Sendai, Japan. nakaik@mail.cc.tohoku.ac.jp
authors: K
authors: K
authors: Nakai
authors: H
authors: H
authors: Togashi
authors: T
authors: T
authors: Yasukohchi
authors: I
authors: I
authors: Sakuma
authors: S
authors: S
authors: Fujii
authors: M
authors: M
authors: Yoshioka
authors: H
authors: H
authors: Satoh
authors: A
authors: A
authors: Kitabatake
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001802:Blood Substitutes / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D004912:Erythrocytes / Q000378:metabolism; D006207:Half-Life; D006454:Hemoglobins / Q000494:pharmacology*; D009569:Nitric Oxide / Q000097:blood; D015538:Nitrosation; D010100:Oxygen / Q000097:blood*; D011092:Polyethylene Glycols / Q000494:pharmacology*; D051381:Rats; D026422:S-Nitrosoglutathione; D013438:Sulfhydryl Compounds
chemical_list: D001802:Blood Substitutes; D006454:Hemoglobins; C109960:PEG-hemoglobin; C103574:S-nitrosohemoglobin; D013438:Sulfhydryl Compounds; D009569:Nitric Oxide; D011092:Polyethylene Glycols; D026422:S-Nitrosoglutathione; D010100:Oxygen