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

Wang,Qi-Wen; Wang,Yi; Wang,Tao; Zhang,Kang-Bao; Yuan,Yan; Bian,Jian‑Chun; Liu,Xue-Zhong; Gu,Jian-Hong; Zhu,Jia-Qiao; Liu,Zong-Ping

doi:10.3892/mmr.2015.3907

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

Authors:
- 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
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Affiliations: College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, P.R. China
Published online on: June 11, 2015 https://doi.org/10.3892/mmr.2015.3907
Pages: 4448-4454

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Abstract

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 autophagy (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.

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