NQO1 Deficiency Leads Enhanced Autophagy in Cisplatin-Induced Acute Kidney Injury Through the AMPK/TSC2/mTOR Signaling Pathway.

Abstract Aims: Recent studies have revealed that autophagy is induced under various disease conditions; however, the role of autophagy in pathological states is controversial. NAD(P)H:quinone oxidoreductase 1 (NQO1) is a highly inducible cytoprotective gene that regulates reactive oxygen species (ROS) generation. In this study, we examined whether NQO1 deficiency affects the autophagy process in response to cisplatin-induced nephrotoxicity. Results: In vitro, NQO1 and autophagy-associated proteins were induced after cisplatin treatment and the autophagosomes markedly increased in the cisplatin-treated NQO1-knockdown ACHN cells together with increased ROS production. In vivo, NQO1-KO mice displayed a significant increase in cisplatin-induced acute kidney injury (AKI), as indicated by elevated tubular damage and apoptosis as well as by suppressed cytoprotective signals. In agreement with the in vitro findings, NQO1-KO cisplatin-treated mice displayed a notable increase in autophagy-associated protein expres...