Preprint Article Version 1 This version is not peer-reviewed

Crosstalk between Autophagy and Apoptosis Modulates T-2 Toxin-Induced Toxicity in Liver Cells

Version 1 : Received: 2 October 2018 / Approved: 2 October 2018 / Online: 2 October 2018 (16:51:09 CEST)

How to cite: Wu, J.; Zhou, Y.; Yuan, Z.; Yi, J.; Chen, J.; Wang, N.; tian, Y. Crosstalk between Autophagy and Apoptosis Modulates T-2 Toxin-Induced Toxicity in Liver Cells. Preprints 2018, 2018100034 (doi: 10.20944/preprints201810.0034.v1). Wu, J.; Zhou, Y.; Yuan, Z.; Yi, J.; Chen, J.; Wang, N.; tian, Y. Crosstalk between Autophagy and Apoptosis Modulates T-2 Toxin-Induced Toxicity in Liver Cells. Preprints 2018, 2018100034 (doi: 10.20944/preprints201810.0034.v1).

Abstract

T-2 toxin produced by fungi of Fusarium genus is highly toxic to human and animals and has been shown to induce apoptosis in various organs/tissues. Apoptosis and autophagy are interconnected processes and these interactions are important for cellular homeostasis as well as pathogenesis. In this study, we report for the first time that T-2 toxin induced autophagy in human liver cells (L02). We showed that T-2 toxin induced the formation of acidic vesicular organelles, concordant with the time and dose-dependent alterations in LC3-phosphatidylethanolamine conjugate (LC3-II) LC3-I/II and p62/SQSTM1 suggesting an enhanced autophagic flux. The T-2 toxin-induced formation of autophagosome and lysosomal fusion was observed by expressing mRFP-GFP-LC3 in L02 cells by lentiviral transduction, and autophagosome was observed by transmission electron microcopy. We found that while T-2 toxin activated both apoptosis and autophagy, activation of autophagy appears to be a leading event reflecting the protective mechanism of cells against the insults by T-2 toxin. Activating autophagy by rapamycin (RAPA) inhibited the apoptosis while suppressing autophagy by chloroquine greatly enhanced the T-2 toxin-induced apoptosis suggesting the crosstalk of autophagy and apoptosis. In summary, our study showed that activation of autophagy protects liver cells from T-2 toxin-induced apoptosis suggesting autophagy may be targeted for prevention of the T-2 toxin-induced toxicity in human and animals.

Subject Areas

T-2 toxin, toxicity, autophagy, apoptosis

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