线粒体呼吸链抑制剂对青蒿素代谢速率的影响  

Effect of mitochondrial electron transport inhibitors on the metabolic rate of artemisinin

作　　者：王娟[1] 周兵[1] 

机构地区：[1]清华大学生物科学与技术系,北京100084

出　　处：《清华大学学报（自然科学版）》2010年第6期944-946,共3页Journal of Tsinghua University(Science and Technology)

基　　金：国家杰出青年科学基金资助项目(30688001)

摘　　要：线粒体呼吸链在青蒿素抑制酵母的过程中起重要作用。为了研究线粒体呼吸链对青蒿素代谢的影响,利用不同的抑制剂抑制线粒体呼吸链,用薄层层析法检测青蒿素代谢速率。结果表明:还原型烟酰胺腺嘌呤二核苷酸(NADH)脱氢酶抑制剂(DPI)可以减缓酵母细胞和疟原虫细胞对青蒿素的代谢,而呼吸链复合物Ⅱ、Ⅲ、Ⅳ的抑制剂对青蒿素消耗没有明显影响。NADH脱氢酶在青蒿素代谢中起重要作用,NADH脱氢酶结构上存在巨大差异。这也为解释青蒿素的物种选择性毒性提供了线索。Mitochondria are the main target of artemisinin in yeast（Saccharomyces cerevisiae） and the mitochondrial electron transport chain plays an important role in the action of artemisinin.Inhibitors of the electron transport chain and thin layer chromatography were used to study the role of the mitochondrial electron transport chain in the metabolism of artmisinin in cells.The results show that Diphenylene iodonium（DPI）,an inhibitor of reduced nicotinamide adenine dinucleotide（NADH） dehydrogenase in the mitochondrial electron transport chain,slowed artemisinin metabolism in both yeast and malaria parasites while inhibitors of other complexes（complex Ⅱ,Ⅲ,Ⅳ） in electron transport chain did not.The data provides evidence of the metabolic aspects for the role of NADH dehydrogenase in the action of artemisinin.The various structures of NADH dehydrogenase of mammalian cells and yeast or malaria parasites were analyzed to explain the organism specific toxicity of artemisinin.

关 键 词：酵母 疟原虫 青蒿素 线粒体 呼吸链 

分 类 号：R38[医药卫生—医学寄生虫学]