Atg7 mediates renal tubular cell apoptosis in vancomycin nephrotoxicity through activation of PKC‐δ

• DOI: 10.1096/fj.201801515r
• Publication Date: 2018-12-27T18:54:52Z
• Authors: Xuan Xu; Jian Pan; Huiling Li; Xiaozhou Li; Fang Fang; Dengke Wu; Yu Zhou; Peiling Zheng; Li Xiong; Dongshan Zhang
• Keywords: Nephrotoxicity

Recent studies have shown that autophagy exhibits a renoprotective role in various models of acute kidney injury (AKI). However, its vancomycin (Van)-induced AKI remains largely unclarified. This study was the first to indicate rapidly activated both human kidney-2 cells and renal tissues, mammalian target rapamycin (mTOR) inactivated via suppression ERK1/2 mTOR during Van treatment. Interestingly, for vitro vivo experiments, chloroquine PT-Atg7-KO significantly ameliorated Van-induced tubular cell apoptosis. Global gene expression analysis indicated levels 6159 genes were induced by treatment cortical tissues PT-Atg7 wild-type mice, 18 them notably suppressed mice. These further classified as programmed death, protein binding, signal transduction, E3 ubiquitin ligase, nucleoside diphosphate kinase activity, E1-like activating enzyme. Unexpectedly, following treatment, PKC-δ found be highest among 4 related which remarkably In addition, Atg7 could induce apoptosis binding PKC-δ. Likewise, inhibition PKCδ tissues. Furthermore, data showed exerted effect against nephrotoxicity, but this lost after injection with myc-tagged PKCδ. Taken altogether, these results induces suppressing activation signaling pathway. mediates through sum, may serve novel therapeutic treating nephrotoxic Van.-Xu, X., Pan, J., Li, H., Fang, F., Wu, D., Zhou, Y., Zheng, P., Xiong, L., Zhang, D. nephrotoxicity