Saxifragifolin D attenuates phagosome maturation arrest in Mycobacterium tuberculosis-infected macrophages via an AMPK and VPS34-dependent pathway.
Saxifragifolin D attenuates phagosome maturation arrest in Mycobacterium tuberculosis-infected macrophages via an AMPK and VPS34-dependent pathway.
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Saxifragifolin D 通过 AMPK 和 VPS34 依赖性途径减弱结核分枝杆菌感染的巨噬细胞中的吞噬体成熟停滞。
DOI：
10.1186/s13568-016-0317-6
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发表时间：
2017-12
期刊：
影响因子：
3.7
通讯作者：
Li Q
中科院分区：
文献类型：
--
作者：
Zhou J;Xu R;Du XZ;Zhou XD;Li Q
Saxifragifolin D （SD）是一种首次从伞花仙子中分离得到的五环三萜化合物，是一种中药。据报道，多种植物三萜具有抗结核活性。在这项研究中，thp -1来源的巨噬细胞被减毒结核分枝杆菌H37Ra感染。培养4周后，通过计数菌落来评估结核分枝杆菌的细胞内复制。结果表明，SD处理可减少thp -1来源的巨噬细胞内M.tb的复制，但在A549细胞中没有。我们使用共聚焦显微镜进行了吞噬体成熟试验，发现SD治疗部分减弱了结核分枝杆菌感染引起的吞噬体停滞。这些作用依赖于vps34相关通路。免疫沉淀实验显示，SD增加了细胞内uvrag连接的VPS34，活性VPS34复合物II。然而，SD对总VPS34池没有影响。此外，结果表明sd介导的VPS34复合物II活性的增加是通过ampk依赖性途径介导的。总的来说，这些数据表明SD可能是治疗结核分枝杆菌的有希望的候选药物。
Saxifragifolin D (SD), a traditional Chinese medicine, is a pentacyclic triterpenoid compound first isolated from Androsace umbellata. Various plant triterpenoids have been reported to exhibit antitubercular activity. In this study, THP-1-derived macrophages were infected with an attenuated M. tuberculosis (M.tb) strain, H37Ra. Intracellular replication of M.tb was evaluated by counting the colonies after 4 weeks of incubation. The results indicated that SD treatment reduced the intracellular replication of M.tb in THP-1-derived macrophages but not in A549 cells. We performed a phagosome maturation test using confocal microscopy and found that SD treatment partially attenuated the phagosome arrest induced by M.tb infection. These effects were dependent on a VPS34-associated pathway. Immunoprecipitation assays showed that SD increased intracellular UVRAG-linked VPS34, the active VPS34 complex II. However, SD had no effect on the total VPS34 pool. Moreover, the results indicated that the SD-mediated increase in VPS34 complex II activity was mediated by an AMPK-dependent pathway. Collectively, these data indicate that SD may be a promising candidate for treatment of M.tb.