Indanostatin, a new neuroprotective compound from Streptomyces sp.
Indanostatin, a new neuroprotective compound from Streptomyces sp.
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DOI：
10.1038/ja.2013.80
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发表时间：
2013-12-01
影响因子：
3.3
通讯作者：
Izawa, Masumi
中科院分区：
文献类型：
--
作者：
Hayakawa, Yoichi;Kobayashi, Toshio;Izawa, Masumi
脑缺血是全世界死亡和长期残疾的主要原因。在脑缺血时，血流中断限制了神经元的氧气和葡萄糖供应，引发兴奋性毒性事件。这些包括谷氨酸受体的激活和过量谷氨酸的释放。它们诱导神经元去极化和细胞内钙的显着增加，从而激活多种细胞内死亡途径。 1 细胞外谷氨酸的积累也会抑制胱氨酸-谷氨酸交换器，导致细胞内抗氧化剂谷胱甘肽的消耗。 2, 3 在这种情况下，会产生活性氧并导致神经元细胞死亡。 4C6神经胶质瘤细胞最初来源于N-亚硝基甲基脲诱导的大鼠神经肿瘤。 5 这些细胞仍然保持神经胶质细胞的特征，并在接触谷氨酸时发生细胞死亡。因此，它们为评估针对谷氨酸毒性的神经保护活性提供了一个良好的模型。据报道，包括抗氧化剂在内的多种化学物质可抑制谷氨酸诱导的 C6 细胞细胞毒性。 6-8 在这项研究中，筛选微生物代谢物以寻找针对谷氨酸毒性的神经保护化合物。结果，从链霉菌培养液中分离出一种新的活性化合物，命名为茚达他汀 (1)。 RAI20。
Cerebral ischemia is a leading cause of death and long-term disabilities worldwide. In brain ischemia, blood flow disruptions limit the supply of oxygen and glucose to neurons, initiating excitotoxic events. These include activation of glutamate receptors and release of excess glutamate. They induce neuron depolarization and significant increase of intracellular calcium, which activates multiple intracellular death pathways. 1 Accumulation of extracellular glutamate also inhibits cystine-glutamate exchanger, resulting in depletion of the intracellular antioxidant glutathione. 2, 3 In such conditions, reactive oxygen species are generated and implicated in neuronal cell death. 4C6 glioma cells were originally derived from rat neural tumors induced by N-nitrosomethylurea. 5 The cells still maintain the characteristics of glial cells and undergo cell death when exposed to glutamate. Thus, they provide a good model for evaluating neuroprotective activity against glutamate toxicity. Several chemicals including antioxidants have been reported to inhibit glutamateinduced cytotoxicity in C6 cells. 6–8 In this study, microbial metabolites were screened to find neuroprotective compounds against glutamate toxicity. As a result, a new active compound designated indanostatin (1) was isolated from the cultured broth of Streptomyces sp. RAI20.