Cucurbitacin B Exerts Antiaging Effects in Yeast by Regulating Autophagy and Oxidative Stress
Cucurbitacin B Exerts Antiaging Effects in Yeast by Regulating Autophagy and Oxidative Stress
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葫芦素 B 通过调节自噬和氧化应激在酵母中发挥抗衰老作用
DOI：
10.1155/2019/4517091
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发表时间：
2019-01-01
影响因子：
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通讯作者：
Qi, Jianhua
中科院分区：
文献类型：
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作者：
Lin, Yanfei;Kotakeyama, Yuki;Qi, Jianhua
芽殖酵母酿酒酵母（Saccharomyces cerevisiae）已被用作衰老基本机制的模式生物，这为测量复制和时序寿命提供了有用的测定系统。在我们筛选延长复制寿命的物质的过程中，葫芦素B（Cu B）被发现是我们研究组从天然产物中分离的化合物库中的一个热门化合物，该化合物库包含皂苷、酚类、倍半萜类、三萜类和甾醇。重要的是，它不仅延长了复制寿命，而且延长了酵母的时间寿命。CuB增加ATG 32基因表达，表明CuB诱导自噬。事实上，由GFP-Atg 8切割产生的GFP信号（其是自噬的标志）在CuB处理后增加。另一方面，当缺失必需的自噬基因ATG 2或ATG 32时，CuB未能增加时间寿命，表明CuB的寿命延长依赖于自噬诱导。此外，CuB还能显著提高氧化胁迫下酵母菌的SOD活性和存活率，降低活性氧（ROS）和丙二醛（MDA）的生成量，表明CuB具有抗氧化胁迫的活性。此外，CuB没有影响复制寿命的sod 1，sod 2，uth 1和skn 7突变体与K6001的背景，表明衰老相关基因，包括SOD 1，SOD 2，UTH 1和SKN 7参与的CuB的抗衰老作用。这些结果表明，CuB通过调节自噬、ROS、抗氧化能力和衰老相关基因发挥抗衰老活性。最后，我们讨论了可能的细胞内目标的CuB的基础上的表型比较的CuB和全球基因缺失数据库。
The budding yeast Saccharomyces cerevisiae has been used as a model organism for the basic mechanism of aging, which provides useful assay systems for measuring both replicative and chronological lifespans. In the course of our screening program for substances that extend replicative lifespan, cucurbitacin B (CuB) was found as a hit compound from a compound library, which contains cerebrosides, phenols, sesquiterpenoid, triterpenoids, and sterols isolated from natural products by our research group. Importantly, it prolonged not only the replicative lifespan but also the chronological lifespan in yeast. CuB increased ATG32 gene expression, suggesting that CuB induces autophagy. Indeed, the GFP signal generated from the cleavage of GFP-Atg8, which is a signature of autophagy, was increased upon CuB treatment. On the other hand, CuB failed to increase the chronological lifespans when either ATG2 or ATG32, essential autophagy genes, was deleted, indicating that the lifespan extension by CuB depends on autophagy induction. Furthermore, CuB significantly increased superoxide dismutase (Sod) activity and the survival rate of yeast under oxidative stress, while it decreased the amount of reactive oxygen species (ROS) and malondialdehyde (MDA) production, indicating that CuB has activity to antagonize oxidative stress. Additionally, CuB did not affect replicative lifespans of sod1, sod2, uth1, and skn7 mutants with the K6001 background, indicating that aging-related genes including SOD1, SOD2, UTH1, and SKN7 participate in the antiaging effect of CuB. These results suggest that CuB exerts antiaging activity by regulating autophagy, ROS, antioxidative ability, and aging-related genes. Finally, we discuss the possible intracellular targets of CuB based on the phenotypic comparison between the CuB and global gene deletion databases.