Actinopyrone D, a new downregulator of the molecular chaperone GRP78 from Streptomyces sp.
Actinopyrone D, a new downregulator of the molecular chaperone GRP78 from Streptomyces sp.
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DOI：
10.1038/ja.2014.76
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发表时间：
2014-12-01
影响因子：
3.3
通讯作者：
Shin-ya, Kazuo
中科院分区：
文献类型：
--
作者：
Hayakawa, Yoichi;Saito, Junki;Shin-ya, Kazuo
分子伴侣 GRP78 的新下调剂放线菌酮 D 与已知的相关化合物 PM050463 一起从链霉菌中分离出来。拉格92。通过高分辨率FAB-MS确定放线菌酮D的分子式为C25H36O4。 NMR光谱分析揭示了actinopyrone D的结构，其由α-甲氧基-γ-吡喃酮环和含有顺式烯烃部分的C-17侧链组成。 Actinopyrone D 和 PM050463 剂量依赖性地抑制用含有 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 2-脱氧葡萄糖诱导的荧光素酶表达。 Actinopyrone D 抑制 GRP78 蛋白表达并在内质网应激下诱导细胞死亡。
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 alpha-methoxy-gamma-pyrone ring and a C-17 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.