Inokosterone from Gentiana rigescens Franch Extends the Longevity of Yeast and Mammalian Cells via Antioxidative Stress and Mitophagy Induction.
Inokosterone from Gentiana rigescens Franch Extends the Longevity of Yeast and Mammalian Cells via Antioxidative Stress and Mitophagy Induction.
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来自Gentiana rigescens Franch 的肌诺酮通过抗氧化应激和线粒体自噬诱导延长酵母和哺乳动物细胞的寿命
DOI：
10.3390/antiox11020214
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发表时间：
2022-01-23
期刊：
影响因子：
--
通讯作者：
Qi J
中科院分区：
文献类型：
--
作者：
Liu Y;Liu Q;Chen D;Matsuura A;Xiang L;Qi J
本研究采用酵母复制寿命和时间寿命试验对中草药滇龙胆抗衰老活性成分进行了双筛选。从G. rigescens Franch不仅延长了K6001酵母的复制寿命，而且延长了YOM 36酵母的时间寿命。此外，它还能增强哺乳动物细胞的存活能力。为了了解该化合物的作用机制，本研究在进行分析时侧重于抗氧化应激和自噬。在肌醇甾酮处理组中观察到氧化应激条件下细胞存活率、抗氧化酶活性和基因表达的增加。同时，活性氧（ROS）和脂质过氧化反应也明显降低。此外，YOM 38-GFP-ATG 8酵母中的巨自噬和线粒体自噬在肌醇甾酮处理后分别增加。与此同时，在细胞质中GFP-ATG 8的无切割GFP和蛋白质水平上线粒体的泛素在与inokosterone孵育后显著增强。此外，我们还研究了肌醇甾酮对哺乳动物细胞抗氧化应激和自噬的影响，以及ROS与自噬的关系。经肌醇甾酮处理后，细胞内活性氧、丙二醛（MDA）含量明显降低，自噬体数量明显增加。在K6001背景下，自噬体无明显变化，但ROS和MDA含量较K6001酵母有所增加。结果表明，经肌醇甾酮处理后，酵母细胞自噬体数量增加，ROS和MDA含量降低。同时，在用肌醇甾酮处理后，观察到缺乏自噬的K6001酵母的ROS水平降低和SOD 1基因表达增加。为了探讨抗氧化酶和自噬相关基因是否参与了肌醇甾酮的抗衰老作用，构建了K6001酵母突变体，进行了寿命测定。对K6001酵母菌的Bisod 1、Bisod 2、Bisuth 1、Bisskn 7、Bisgpx、Biscat、Bisatg 2和Bisatg 32的复制寿命无影响。这些结果表明，inokosterone通过抗氧化应激和增加自噬激活发挥抗衰老活性;自噬通过调节SOD 1基因表达影响酵母的ROS水平。
In the present study, replicative lifespan and chronological lifespan assays of yeast were used to double-screen antiaging compounds from Gentiana rigescens Franch, a Chinese herb medicine. Inokosterone from G. rigescens Franch extended not only the replicative lifespan of K6001 yeast but also the chronological lifespan of YOM36 yeast. Furthermore, it can enhance the survival ability of mammalian cells. In order to understand the mechanism of action of this compound, this study focused on antioxidative stress and autophagy when performing the analysis. The increased cell survival rate under oxidative stress conditions, antioxidant enzyme activity and gene expression were observed in the inokosterone-treated groups. Meanwhile, the reactive oxygen species (ROS) and lipid peroxidation of yeast were obviously decreased. Additionally, the macroautophagy and mitophagy in YOM38-GFP-ATG8 yeast were increased upon inokosterone treatment, respectively. At the same time, the cleavage-free GFP from GFP-ATG8 in the cytoplasm and the ubiquitin of the mitochondria at the protein level were markedly enhanced after incubation with inokosterone. Furthermore, we investigated the effect of inokosterone on antioxidative stress and autophagy in mammalian cells, and the relationship between ROS and autophagy. The ROS, malondialdehyde (MDA) were significantly decreased, and the autophagosomes in mammalian cells were obviously increased after inokosterone treatment. The autophagosomes in ∆sod1 yeast with a K6001 background had no obvious changes, and the ROS and MDA of ∆sod1 yeast were increased compared with K6001 yeast. The increase of autophagosomes and the reduction of ROS and MDA in ∆sod1 yeast were observed after treatment with inokosterone. Meanwhile, the reduction of the ROS level and the increase of the SOD1 gene expression of K6001 yeast lacking autophagy were observed after treatment with inokosterone. In order to indicate whether the genes related to antioxidant enzymes and autophagy were involved in the antiaging effect of inokosterone, mutants of K6001 yeast were constructed to conduct a lifespan assay. The replicative lifespans of ∆sod1, ∆sod2, ∆uth1, ∆skn7, ∆gpx, ∆cat, ∆atg2, and ∆atg32 of K6001 yeast were not affected by inokosterone. These results suggest that inokosterone exerted an antiaging activity via antioxidative stress and increased autophagy activation; autophagy affected the ROS levels of yeast via the regulation of SOD1 gene expression.
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影响因子：
5.6
作者：
Ichimiya T;Yamakawa T;Hirano T;Yokoyama Y;Hayashi Y;Hirayama D;Wagatsuma K;Itoi T;Nakase H
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