期刊
CHEMICO-BIOLOGICAL INTERACTIONS
卷 336, 期 -, 页码 -出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.cbi.2020.109319
关键词
Locoweed; Swainsonine; Apoptosis; Autophagy; Lysosomal
资金
- National Natural Science Foundation of China [32072928]
Research has shown that Swainsonine induces both autophagy and apoptosis in cells, with autophagy playing a protective role. Modulating autophagy can affect the severity of apoptosis in cell damage caused by Swainsonine's toxicity.
Swainsonine (SW), an indolizidine alkaloid, is the primary toxin in locoweeds that causes toxicity syndrome in livestock. Current research shows that SW can induce both apoptosis and autophagy. However, the relationship between, and regulatory mechanism of, autophagy and apoptosis in SW-mediated cytotoxicity remain unclear. In this study, we investigated the role of autophagy and apoptosis in SW-induced cytotoxicity in rat primary renal tubular epithelial cells (RTECs). We examined the effect of SW on lysosomal function using western blotting, transmission electron microscopy, fluorescent microscopy, and flow cytometry. The results showed that SW induced both autophagy and apoptosis, and autophagy protected RTECs from cellular damage. Activating autophagy using rapamycin (Rapa) inhibited apoptosis, while suppressing autophagy using bafilomycin A1 (Baf A1) greatly enhanced SW-induced SW and aloxistatin (E64d) further promoted apoptosis and LC3-II accumulation in RTECs. These results suggest that SW causes toxicity by disrupting lysosomal dysfunction, inhibiting autophagic degradation, and promoting apoptosis.
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