AKT inhibition-mediated dephosphorylation of TFE3 promotes overactive autophagy independent of MTORC1 in cadmium-exposed bone mesenchymal stem cells.

ABSTRACT: Cadmium (Cd) is a toxic metal that is widely found in numerous environmental matrices and induces serious adverse effects in various organs and tissues. Bone tissue seems to be a crucial target of Cd contamination. Macroautophagy/autophagy has been proposed to play a pivotal role in Cd-mediated bone toxicity. However, the mechanisms that underlie Cd-induced autophagy are not yet completely understood. We demonstrated that Cd treatment increased autophagic flux and inhibition of the autophagic process using Atg7 gene silencing blocked the Cd-induced mesenchymal stem cell death. Mechanistically, Cd activated nuclear translocation of TFE3 but not that of TFEB or MITF, which contributed to the expression of autophagy-related genes and lysosomal biogenesis. Specifically, Cd decreased expression

SUBMITTER: Pi H 

PROVIDER: S-EPMC6526814 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature