From the Cover: Autophagy Induction Contributes to Cadmium Toxicity in Mesenchymal Stem Cells via AMPK/FOXO3a/BECN1 Signaling

This study investigated the role of autophagy in Cd-induced skeleton damage and its potential mechanism. We exposed MSCs to different concentrations of cadmium chloride (3.5, 7, and 14 μM) for 24 h. We demonstrated that Cd treatment increased autophagic flux, and inhibition of autophagic process using BENC1 gene silencing blocked Cd-induced cell death. Cd treatment also significantly increased mRNA levels of various essential autophagy-related genes including ATG5, ATG12, BECN1, LC3, and ULK1. Specifically, Cd increased FOXO3a and FOXO1 expression at the mRNA and protein levels, and AMPK was demonstrated to enhance FOXO3a nuclear translocation and transcriptional activity by phosphorylating FOXO3a at specific serine residues (Ser588) in Cd-treated MSCs. Notably, knockdown of FOXO3a, but not FOXO1, prevented autophagy-related genes expression and autophagosome formation after Cd treatment. Taken together, our results demonstrate that Cd-induced cell death via the overactivation of FOXO3a-dependent autophagy. Modulation of the FOXO3a autophagy pathway may offer novel therapeutic approaches for the treatment of Cd-induced bone damage.

Source: Toxicological Sciences - October 27, 2016 Category: Toxicology Authors: Yang, M., Pi, H., Li, M., Xu, S., Zhang, L., Xie, J., Tian, L., Tu, M., He, M., Lu, Y., Yu, Z., Zhou, Z. Tags: Cadmium and Autophagy in Mesenchymal Stem Cells Source Type: research