Hayakawa Yoichi, Saito Junki, Izawa Masumi, Shin-ya Kazuo
Faculty of Pharmaceutical Sciences, Department of Medicinal and Life Science, Tokyo University of Science, Chiba, Japan.
Biological Information Research Center, National Institute of Advanced Industrial Science and Technology, Tokyo, Japan.
J Antibiot (Tokyo). 2014 Dec;67(12):831-4. doi: 10.1038/ja.2014.76. Epub 2014 Jun 18.
A new downregulator of the molecular chaperone GRP78, actinopyrone D, was isolated together with a known related compound, PM050463, from Streptomyces sp. RAG92. The molecular formula of actinopyrone D was established as C25H36O4 by high-resolution FAB-MS. NMR spectroscopic analysis revealed the structure of actinopyrone D, which consists of an α-methoxy-γ-pyrone ring and a C17 side chain containing a cis olefin moiety. Actinopyrone D and PM050463 dose-dependently inhibited 2-deoxyglucose-induced luciferase expression in HT1080 human fibrosarcoma cells transfected with a luciferase reporter plasmid containing the GRP78 promoter. Actinopyrone D inhibited GRP78 protein expression and induced cell death under endoplasmic reticulum stress.
从链霉菌属RAG92中分离出一种新的分子伴侣GRP78的下调剂放线菌酮D，以及一种已知的相关化合物PM050463。通过高分辨率FAB-MS确定放线菌酮D的分子式为C25H36O4。核磁共振光谱分析揭示了放线菌酮D的结构，它由一个α-甲氧基-γ-吡喃酮环和一个含有顺式烯烃部分的C17侧链组成。放线菌酮D和PM050463在含有GRP78启动子的荧光素酶报告质粒转染的HT1080人纤维肉瘤细胞中，剂量依赖性地抑制2-脱氧葡萄糖诱导的荧光素酶表达。放线菌酮D在内质网应激条件下抑制GRP78蛋白表达并诱导细胞死亡。
