仿生信号转导体系的构建:囊泡表面磷脂信号分子诱发的乳酸脱氢酶的激活

化学学报 ›› 2004, Vol. 62 ›› Issue (13): 1230-1236. 上一篇下一篇

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仿生信号转导体系的构建:囊泡表面磷脂信号分子诱发的乳酸脱氢酶的激活

田文杰^1,2, 佐佐木善浩¹, 池田笃志¹, 菊池纯一¹, 宋溪明³, 范圣第²

1. 日本奈良先端科学技术大学院大学物质创成科学研究科, 奈良, 630-0192;
2. 大连民族学院生物工程系, 大连, 116600;
3. 辽宁大学化学科学与工程学院, 沈阳, 110036

投稿日期:2003-12-11 修回日期:2004-03-15 发布日期:2014-02-17
通讯作者: 田文杰,菊池纯一,E-mail:jkikuchi@ms.naist.jp;Fax:+81-743-72-6099 E-mail:jkikuchi@ms.naist.jp
基金资助:
日本学术振兴会科学研究基金(No.15205022,2003)资助项目.

Construction of a Bio-inspired Signal Transduction System: Activation of Lactate Dehydrogenase Triggered by Lipid Signal Molecules on Bilayer Vesicles

TIAN Wen-Jie^1,2, SASAKI Yoshihiro¹, IKEDA Atsushi¹, KIKUCHI Jun-ichi¹, SONG Xi-Ming³, FAN Sheng-Di²

1. Graduate School of Materials Science, Nara Institute of Science and Technology, Nara 630-0192, Japan;
2. Department of Biological Engineering, Dalian Nationalities University, Dalian 116600, China;
3. School of Chemical Science and Engineering, Liaoning University, Shenyang 110036, China

Received:2003-12-11 Revised:2004-03-15 Published:2014-02-17

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摘要/Abstract

以细胞肌醇磷脂信号转导途径为原型,在合成肽脂囊泡(人工细胞膜模型)上,利用天然磷脂为信号分子,成功地激活了处于囊泡表面的乳酸脱氢酶.为此,将1,2-二-十四烷基磷脂酰乙醇胺等天然磷脂嵌入合成肽脂N,N-二-十六烷基-N^a-6-三甲胺基己酰基-L-甘氨酰胺囊泡中,制备了稳定的混合双层膜囊泡,用透射电子显微照相、动态光散射及差示扫描量热等手段确认了混合囊泡的形态及粒径分布.以磷酸吡哆醛等维生素B₆类化合物为信号分子激活剂,利用它们与天然磷脂形成复合体,进而与Cu²⁺形成强的金属配合物的性质,实现了对处于囊泡表面、被Cu²⁺抑制的乳酸脱氢酶的激活,构建了一个新的仿生信号转导体系.紫外-可见光谱实验证实了以上结果.此外,结果还表明囊泡表面的疏水作用和静电引力是促进天然磷脂-磷酸吡哆醛复合体形成的主要因素.囊泡表面的疏水微环境作为反应场是构建此仿生信号转导体系不可缺少的要素.

关键词: 磷脂信号分子, 囊泡, 乳酸脱氢酶, 仿生信号转导

An artificial signal transduction system, in which an enzymatic activity was controlled by a lipid signal embedded in a biomembrane model, was constructed.The system was inspired by the biological phosphoinositide (PI)-triggered signal transduction.For this propose, hybrid bilayer vesicles with a mean diameter of 100 nm were formed by combination of dimyristylphosphatidylethanolamine as a lipid signal moiety and a cationic synthetic lipid as a matrix.The aggregate morphology was confirmed by means of transmission electron microscopy and dynamic light scatting measurements, and the vesicles showed a phase transition from gel to liquid-crystalline state at 31.2℃ as evaluated with differential scanning calorimetry.On the cationic vesicular surface, the lipid signal specifically recognized pyridoxal 5'-phosphate as a signal activator to form a signal-signal activator complex.The hydrophobic and the electrostatic interactions were much enhanced in the microenvironment on the vesicular surface to form the binary complex.The resulting binary complex exhibited extremely high binding affinity toward Cu²⁺ ions.Thus, the catalytic activity of lactate dehydrogenase, which was inhibited by binding of Cu²⁺ ion to the enzyme active site on bilayer vesicles, was effectively recovered upon formation of the signal-signal activator complex, reflecting that the binding affinity of the signal-signal activator complex with Cu²⁺ ion overcame that of the enzyme.

Key words: phospholipid signal, vesicle, lactate dehydrogenase, bio-inspired signal transduction

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田文杰, 佐佐木善浩, 池田笃志, 菊池纯一, 宋溪明, 范圣第. 仿生信号转导体系的构建:囊泡表面磷脂信号分子诱发的乳酸脱氢酶的激活[J]. 化学学报, 2004, 62(13): 1230-1236.

TIAN Wen-Jie, SASAKI Yoshihiro, IKEDA Atsushi, KIKUCHI Jun-ichi, SONG Xi-Ming, FAN Sheng-Di. Construction of a Bio-inspired Signal Transduction System: Activation of Lactate Dehydrogenase Triggered by Lipid Signal Molecules on Bilayer Vesicles[J]. Acta Chimica Sinica, 2004, 62(13): 1230-1236.

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仿生信号转导体系的构建:囊泡表面磷脂信号分子诱发的乳酸脱氢酶的激活

Construction of a Bio-inspired Signal Transduction System: Activation of Lactate Dehydrogenase Triggered by Lipid Signal Molecules on Bilayer Vesicles

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