Swainsonine induces autophagy via PI3K/AKT/mTOR signaling pathway to injure the renal tubular epithelial cells

Abstract

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.

Keywords: Autophagy; Locoweed; PI3K/Akt/mTOR pathway; Swainsonine; Vacuolar degeneration.