苦马豆素通过 PI3K/AKT/mTOR 信号通路诱导自噬来损伤肾小管上皮细胞。
Swainsonine induces autophagy via PI3K/AKT/mTOR signaling pathway to injure the renal tubular epithelial cells.
机构信息
College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, 712100, China.
State Key Laboratory of Barley and Yak Germplasm Resources and Genetic Improvement, Lhasa, Tibet, 850002, China.
出版信息
Biochimie. 2019 Oct;165:131-140. doi: 10.1016/j.biochi.2019.07.018. Epub 2019 Jul 26.
Swainsonine is a major toxic ingredients of locoweed plants, ingestion of these plants may cause locoism in livestock characterized by extensive cellular vacuolar degeneration of multiple tissues. However, so far, the mechanisms responsible for vacuolar degeneration induced by SW are not known. In this study, we investigated the role of autophagy in SW-induced TCMK-1 cells using Western blotting, transmission electron microscopy, immunofluorescent microscopy and qRT-PCR. The results showed that SW treatment increased the levels of LC3-II. The co-localization of LC3-II and lysosomal protein LAMP-2 results suggested that SW treatment does not interfere with fusion between autophagosome and lysosome. TEM results indicated that SW induced aggregation of the lysosome around the autophagosome. In addition, SW treatment suppressed p-PI3K, p-Akt, p-mTOR, p-p70S6K and p-4EBP1 level. In conclusion, SW induced autophagy via pI3K/AKT/mTOR signaling pathway and revealed the role of autophagy in causing the SW toxicity characterized by the vacuolar degeneration.
苦马豆素是疯草植物的主要毒性成分，摄入这些植物可能会导致牲畜出现以广泛的细胞空泡变性为特征的疯草病。然而，到目前为止，SW 诱导的空泡变性的机制尚不清楚。在这项研究中，我们使用 Western blot、透射电子显微镜、免疫荧光显微镜和 qRT-PCR 研究了自噬在 SW 诱导的 TCMK-1 细胞中的作用。结果表明，SW 处理增加了 LC3-II 的水平。LC3-II 和溶酶体蛋白 LAMP-2 的共定位表明，SW 处理不干扰自噬体与溶酶体之间的融合。TEM 结果表明，SW 诱导溶酶体在自噬体周围聚集。此外，SW 处理抑制了 p-PI3K、p-Akt、p-mTOR、p-p70S6K 和 p-4EBP1 水平。总之，SW 通过 pI3K/AKT/mTOR 信号通路诱导自噬，并揭示了自噬在导致以空泡变性为特征的 SW 毒性中的作用。
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