Swainsonine promotes apoptosis by impairing lysosomal function and inhibiting autophagic degradation in rat primary renal tubular epithelial cells

  • Chem Biol Interact. 2021 Feb 25;336:109319. doi: 10.1016/j.cbi.2020.109319.
Shuai Wang  1 ,  Rong Guo  1 ,  Yongxia Su  1 ,  Chen Yang  1 ,  Yazhou Guo  1 ,  Chengjian Tan  2 ,  Baoyu Zhao  3
Affiliations
  • 1. College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, 712100, China; Institute of Poisonous Plants in Western China, Northwest A&F University, Yangling, Shaanxi, 712100, China.
  • 2. Department of Biotechnology, Guizhou Medical University, Guiyang, Guizhou, 550004, China.
  • 3. College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, 712100, China; Institute of Poisonous Plants in Western China, Northwest A&F University, Yangling, Shaanxi, 712100, China. Electronic address: [email protected].
PMID: 33186601 DOI: 10.1016/j.cbi.2020.109319
Abstract

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 Apoptosis. SW treatment suppressed the expression of lysosomal-related proteins, and co-incubation with 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.

Keywords
Apoptosis; Autophagy; Locoweed; Lysosomal; Swainsonine.
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