Efrapeptin J, a new down-regulator of the molecular chaperone GRP78 from a marine Tolypocladium sp.
Efrapeptin J, a new down-regulator of the molecular chaperone GRP78 from a marine Tolypocladium sp.
复制标题
DOI：
10.1038/ja.2008.51
复制
发表时间：
2008-06-01
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;Hattori, Yuki;Shin-ya, Kazuo
从海洋真菌toolypocladium sp. amb18中分离到一种新的GRP78分子伴侣下调因子efrapeptin J。通过高分辨率FAB-MS确定efrapeptin J的分子式为C81H139N18O16+。经核磁共振和质谱分析证实，该结构为线性五肽，含有六氢吡咯[1,2-a]嘧啶基团。efrapeptin F， G和J剂量依赖性地抑制2-脱氧葡萄糖诱导的HT1080人纤维肉瘤细胞中含有GRP78启动子的荧光素酶报告质粒转染的荧光素酶表达。Efrapeptin J对HT1080细胞和MKN-74人胃癌细胞中GRP78蛋白的表达也有抑制作用。Efrapeptin J诱导内质网应激下HT1080细胞死亡。
A new down-regulator of the molecular chaperone GRP78, efrapeptin J, was isolated from a marine fungus, Tolypocladium sp. AMB 18. The molecular formula of efrapeptin J was established as C81H139N18O16+ by high-resolution FAB-MS. The structure was elucidated to be a linear pentadecapeptide containing a hexahydropyrrolo[1,2-a]pyrimidinium moiety by NMR and MS analyses. Efrapeptins F, G and J dose-dependently inhibited 2-deoxyglucose-induced luciferase expression in HT1080 human fibrosarcoma cells transfected with a luciferase reporter plasmid containing the GRP78 promoter. Efrapeptin J also inhibited the protein expression of GRP78 in HT1080 cells and MKN-74 human gastric cancer cells. Efrapeptin J induced cell death in HT1080 cells under endoplasmic reticulum stress.