Construction of Hemoglobin-vesicle with long-term in vivo oxygen transporting ability

具有体内长期输氧能力的血红蛋白囊泡的构建

• 批准号: 18500368
• 负责人: TAKEOKA Shinji
• 金额: $ 1.33万
• 依托单位: Waseda University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18500368/
• 关键词: Hemoglobin; Hemoglobin-vesicle; Artificial oxygen carrier; metHb formation; Tyrosine; Peroxidase; Hydrogen peroxide; Carbonylation; 人工臓器学; 生体機能材料; 薬物送達システム; 酵素化学; 生体系類似化学; 酵素とタンパク質

The hemoglobin vesicles (HbV) encapsulating hemoglobin (Hb), which binds oxygen reversibly, in the phospholipid vesicle (liposome) function as an artificial oxygen carrier. However, Hb loses an oxygen binding capacity when central iron is oxidized from two valences to three (metHb formation). In this phenomenon, metHb formation (autoxidation) by one electron transfer from the central iron to the bound oxygen and the further metHb formation by the resulting reactive oxygen (peroxide) are taken place in a row. We have found out that a (metHb Hb/L-tyrosine) system eliminates peroxide promptly. In present study, it was confirmed that the hydrogen peroxide elimination system utilizing the peroxidase activity of metHb which uses L-tyrosine as a substrate was effective for suppression of metHb formation. Moreover, we confirmed the remarkable suppression of metHb formation of HbV which included this system in their inner aqueous phase, even if hydrogen peroxide were continuously added to the H … More bV dispersion. When the 20mL/kg of the HbV dispersion was administrated into rats, the half time of metHb formation in this HbV extended till 44 hours in comparison with 14 hours of the conventional HbV. Furthermore, from a novel screening method which measured the reaction rate of ferryl Hb radical with 14 kinds of candidate substances other than Tyr, we found that some derivatives which possesses indore rings such as tryptophane or carboxyl groups showed the suppressive effect higher than Tyr.On the other hand, metHb formation caused from autoxidation does not occur for carbonyl Hb (HbCO). And if we use the phenomenon of the gradual conversion of HbCO into HbO_2 in blood circulation, we can maintain an oxygen carrying capacity by suppressing the metHb formation of HbV containing HbCO. In present study, we measured the change of the metHb formation rate of HbV containing HbCO and clarified that the rate of metHb from the remaining HbO_2 was the same in spite of the differed portion of HbCO. Therefore, it is suggested that gentle metHb formation system can be constructed in accompanied with the elimination of CO from HbCO. As mentioned above, if these dual approaches are paired, it is expected that the metHb formation of HbV can be effectively controlled by in vivo. Less

封装血红蛋白（HB）的血红蛋白蔬菜（HBV），在磷脂蔬菜（脂质体）中可逆地结合氧气作为人造氧载体。但是，当中央铁从两个价值氧化到三个（MECHB形成）时，HB失去了氧结合能力。在这种现象中，通过一个电子从中央铁转移到结合氧的电子传递，并通过产生的活性氧（过氧化氧化物）的进一步甲基形成。我们发现（甲基HB/L型苯胺）系统迅速消除了过氧化剂。在目前的研究中，已经证实，过氧化氢发射系统利用使用L-酪氨酸作为底物的MECHB的过氧化物酶活性有效地抑制了甲壳的形成。此外，我们证实了HBV的MECHB形成的显着抑制，即即使将过氧化氢连续添加到H…更多BV分散体中，该系统包括该系统内的水相中。当HBV分散体的20mL/kg在行政上分解为大鼠时，与常规HBV相比，该HBV中的MECHB形成的半个时间延长至44小时。此外，从一种新型筛选方法中，通过除了Tyr以外的14种候选物质的Ferryl HB激进分子的反应速率，我们发现某些具有多孔环或羧基等印多环的衍生物表明，抑制效应比Tyr.On.在其他手中高于Tyr，由Autooxidation造成的METH造成的METH B. HB（HB）（HB）（HB）（HBCO）。而且，如果我们在血液循环中使用HBCO级转化为HBO_2的现象，则可以通过抑制含有HBC的HBV的MECHB形成来维持氧气承载能力。在目前的研究中，我们测量了含有HBCO的HBV的MECHB形成速率的变化，并澄清了尽管HBCO的不同部分，其余HBO_2的MECHB速率是相同的。因此，建议可以在从HBCO中消除CO构建温和的METHB形成系统。如上所述，如果将这些双重方法配对，则可以预期HBV的METHB形成可以通过体内有效控制。较少的

项目成果

Analysis of the reduction of ferryl Hemoglobin by L-tyrosine(2)

L-酪氨酸还原铁血红蛋白的分析(2)

• 发表时间: 2006
• 作者: Hirotaka Yatami;Tomoyasu Atoji;Eishun Tsuchida;Shinji Takeoka
• 通讯作者: Shinji Takeoka

Analysis of the reduction of ferryl hemoglobin radical by L-tyrosine and application in hemologbinvesicles

L-酪氨酸还原铁血红蛋白自由基的分析及其在血红蛋白囊泡中的应用

• 发表时间: 2005
• 作者: Tomoyasu Atoji;Hirotaka Yatami;Motonari Aihara;Shinji Takeoka;Eishun Tsuchida
• 通讯作者: Eishun Tsuchida

Encapsulation of concentrated hemoglobin solution in phospholipid vesicles retards the reaction with NO, but not CO, by intracellular diffusion barrier

• DOI: 10.1074/jbc.m707660200
• 发表时间: 2008-01-18
• 期刊: JOURNAL OF BIOLOGICAL CHEMISTRY
• 影响因子: 4.8
• 作者: Sakai, Hiromi;Sato, Atsushi;Tsuchida, Eishun
• 通讯作者: Tsuchida, Eishun

各種代用血漿剤(水溶性高分子)に分散させた人工赤血球(ヘモグロビン小胞体)とその血液混合系のレオロジー特性

分散在各种血浆替代剂（水溶性聚合物）中的人造红细胞（血红蛋白内质网）及其血液混合系统的流变特性

• 发表时间: 2007
• 作者: 佐藤 敦;酒井 宏水;武岡 真司;土田 英俊
• 通讯作者: 土田 英俊

L-チロシンによるフェリルヘモグロビン還元反応の解析(2)

L-酪氨酸还原铁血红蛋白反应的分析（2）

• 发表时间: 2006
• 作者: 谷田海博孝;阿閉友保;土田英俊;武岡真司
• 通讯作者: 武岡真司