Application of plasma proteins as blood substitutes

血浆蛋白作为血液代用品的应用

• 批准号: 11794016
• 负责人: NISHI Katsuhide
• 金额: $ 16万
• 依托单位: KUMAMOTO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for University and Society Collaboration
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11794016/
• 关键词: pyridoxalated hemoglobin polyoxyethylene conjugate; α_1-acid glycoprotein; S-nitrosylation; human serum albumin; recombinant human serum albumin; cytochrome b562; 酸化アルブミン; Cys残基; ミオグロビン; 配位子結合性; α-1酸性糖タンパク; 細隙通過促進作用; 微細循環改善作用; 白血球走化性抑制作用; 炎症

Nishi et al. found the inhibitory effects of pyridoxalated hemoglobin polyoxyethylene conjugate (PHP) on the intestinal peristaltic movement, the facilitatory effect of α_1-acid glycoprotein (α_1-AGP) on the passage of red blood cells through filters with micropores, and the vasodilator action of α_1-AGP in aorta.Maeda et al. found that S-nitrosylation of α_1-protease inhibitor (α_1-PI) occurring under physiological conditions should diverse in the biological functions contributing to cytoprotective effects of α_1-PI, and suggested that S-nitrosylated α_1-AGP would have the multiple biological functions.Otagiri et al. purified recombinant human serum albumin (rHSA), secreted by a Pichia pastoris expression system, and showed very similar structural characteristics, stability and ligand-binding properties of the rHSA as HSA isolated from sera.Uno et al. analyzed the amino acid residues surrounding the cofactor in the structures of a four-helix bundle heme protein, cytochrome b562 from E. coli, and developed a strategy for designing an exogenous ligand binding pocket into this protein.

Nishi等发现吡哆醛血红蛋白聚氧乙烯偶联物（PHP）对小肠蠕动的抑制作用，α_1-酸性糖蛋白（α_1-AGP）对红细胞通过微孔滤膜的促进作用，Maeda等发现α_1-蛋白酶抑制剂（α_1-PI）的S-亚硝基化作用与α_1-AGP的血管扩张作用有关。在生理条件下发生的α_1-PI具有多种生物学功能，提示S-亚硝基化α_1-AGP具有多种生物学功能。Otagiri等纯化了毕赤酵母表达系统分泌的重组人血清白蛋白（rHSA），显示出非常相似的结构特征，Uno等分析了来自大肠杆菌的四螺旋束血红素蛋白，细胞色素b562的结构中辅因子周围的氨基酸残基。大肠杆菌，并开发了一种策略，设计一个外源配体结合口袋到这种蛋白质。

项目成果

K.Yamasaki, H.M.Rahman, M.Otagiri, et al.: "Circular Dichroism Simulation shows a Site-II-Site-I Displacement of Human Serum Albumin-bound Diclofenac by Ibuprofen"AAPS Pharm.Sci.Tech.. 1(2). article 12 (2000)

K.Yamasaki、H.M.Rahman、M.Otagiri 等人：“圆二色性模拟显示布洛芬对人血清白蛋白结合的双氯芬酸进行位点 II-位点 I 置换”AAPS Pharm.Sci.Tech.. 1(2

Y.Tsutsumi, T.Maruyama, M.Otagiri, et al.: "Decreased Bilirubin-binding Capacity in Uremic Serum Caused by an Acumulation of Furan Dicarboxylic Acid"Nephron. 85(1). 60-64 (2000)

Y.Tsutsumi、T.Maruyama、M.Otagiri 等人：“呋喃二羧酸积聚导致尿毒症血清胆红素结合能力降低”肾单位。

Tokutomi, Y., Tokutomi, N., Nishi K.: "The properties of ryanodine-sensitive Ca^<2+> release in mouse gastric smooth muscle cells"British Journal of Pharmacology. 133. 125-137 (2001)

Tokutomi，Y.，Tokutomi，N.，Nishi K.：“小鼠胃平滑肌细胞中兰尼碱敏感的Ca ^ 2 释放的特性”英国药理学杂志。

J.Wu, T.Akaike, K.Hayashida, T.Okamoto, A.Okuyama: "Enhanced vascular permeability in solid tumor involving peroxynitrite and matrix metalloproteinase"Jpn.J.Cancer Res.. 92. 439-451 (2001)

J.Wu、T.Akaike、K.Hayashida、T.Okamoto、A.Okuyama：“涉及过氧亚硝酸盐和基质金属蛋白酶的实体瘤中血管通透性增强”Jpn.J.Cancer Res.. 92. 439-451 (2001)

T, Akaike: "Viral mutation accelerated by nitric oxide production during infection in vivo."FASEB J.. 14. 1447-1454 (2000)

T, Akaike：“体内感染过程中一氧化氮的产生加速了病毒突变。”FASEB J.. 14. 1447-1454 (2000)