Cadmium-induced autophagy is mediated by oxidative signaling in PC-12 cells and is associated with cytoprotection

QI-WEN WANG, YI WANG, TAO WANG, KANG-BAO ZHANG, YAN YUAN, JIAN-CHUN BIAN, XUE-ZHONG LIU, JIAN-HONG GU, JIA-QIAO ZHU, ZONG-PING LIU
2015 Molecular Medicine Reports  
Oxidative stress induced by cadmium (Cd) is a common phenomenon that has been observed in numerous studies. However, the underlying mechanism remains unknown. Recently, exposure of PC-12 cells to Cd has been shown to activate autophagy, which acts as a temporary survival pathway under stressful conditions by delaying the occurrence of apoptosis. The present study investigated the impact of oxidative stress on Cd-induced autophagy in PC-12 cells. The results demonstrated that Cd-induced
more » ... (following treatment with Cd for 4 h), increased the levels of intracellular reactive oxygen species (ROS), decreased the mitochondrial membrane potential and resulted in apoptosis. A treatment with chloroquine (CQ; an autophagic inhibitor) sensitized the PC-12 cells to Cd, due to the increased production of ROS, which was associated with the incapacity to reduce mitochondrial and cell death. N-acetyl-L-cysteine, an antioxidant agent, decreased Cd-induced autophagy and reduced intracellular ROS levels, but enhanced CQ-induced apoptotic cell death. These findings indicate that moderate levels of ROS are essential in the regulation of Cd-induced autophagy, which subsequently enhances cell survival. Thus, the results of the present study provide an insight for future investigation of Cd-induced neurotoxicity.
doi:10.3892/mmr.2015.3907 pmid:26062759 fatcat:ydognsfrrfasveuzqlgog5zqfm