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Creation of a Supramolecular CO Receptor for Investigation of Biological Roles of Endogenously-Produced Internal CO

构建超分子 CO 受体用于研究内源产生的内部 CO 的生物学作用

基本信息

批准号：
24750165
负责人：
KITAGISHI Hiroaki
金额：
$ 3万
依托单位：
Doshisha University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Young Scientists (B)
财政年份：
2012
资助国家：
日本
起止时间：
2012 至 2013
项目状态：
已结题

项目摘要

Carbon monoxide (CO) is continuously produced in the eukaryotic organisms during degradation of hemin by heme oxygenase (HO). The biological roles of CO in the living organisms have not been fully understood because of lacking of knockdown method for endogenously produced CO. We have shown that a supramolecular complex, hemoCD, strongly binds CO higher than that of hemoglobin. In the present study, hemoCD was used for removal of CO in the living organisms and genetic response upon removal of CO was investigated. Furthermore, for monitoring the depletion effect of CO in the human cells, the hemoCD scaffold was conjugated with an octaarginine peptide that has a strong ability to bring molecules into the cell interior. This conjugate, R8-hemoCD, was smoothly taken by the HeLa cells without significant toxicities.

血红素加氧酶（HO）降解氯化血红素的过程中，真核生物体内不断产生一氧化碳（CO）。CO在生物体中的生物学作用尚未完全了解，因为缺乏敲低内源性产生的CO的方法。我们已经表明，超分子复合物，hemoCD，强烈结合CO高于血红蛋白。在本研究中，hemoCD用于去除生物体内的CO，并研究了去除CO后的遗传反应。此外，为了监测人细胞中CO的消耗效应，将hemoCD支架与具有将分子带入细胞内部的强能力的八精氨酸肽缀合。该缀合物R8-hemoCD被HeLa细胞顺利摄取，没有显著毒性。