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Autophagy Plays a Cytoprotective Role During Cadmium-Induced Oxidative Damage in Primary Neuronal Cultures

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Abstract

Cadmium (Cd) induces significant oxidative damage in cells. Recently, it was reported that autophagy could be induced by Cd in neurons. However, little is known about the role of reactive oxygen species (ROS) during Cd-induced autophagy. In our study, we examined the cross-talk between ROS and autophagy by using N-acetyl cysteine (NAC, an antioxidant) and chloroquine (CQ, a pharmacological inhibitor of autophagy) in a primary rat neuronal cell cultures. We observed accumulation of acidic vesicular organelles and the increased expression of endogenous protein light chain 3 (LC3) in Cd-treated neurons, revealing that Cd induced a high level of autophagy. Moreover, increased levels of ROS were observed in neurons treated with Cd, showing that ROS accumulation was closely associated with neuron’s exposure to Cd. Furthermore, we found that autophagy was inhibited by using CQ and/or NAC with further aggravation of mitochondrial damage, lactate dehydrogenase (LDH) leakage and hypoploid apoptotic cell number in Cd-treated neurons. These results proved that autophagy has a cytoprotective role during Cd-induced toxicity in neurons, and it can prevent the oxidative damage. These findings may enable the development of novel therapeutic strategies for neurological diseases.

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (31302058, 31101866, 31172373), a Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We are thankful to Dr Maozhi Hu for technical assistance in flow cytometry analysis.

Conflict of Interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009, People’s Republic of China

    Tao Wang, Qiwen Wang, Ruilong Song, Yajing Zhang, Kangbao Zhang, Yan Yuan, Jianchun Bian, Xuezhong Liu, Jianhong Gu & Zongping Liu

  2. Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, 225009, People’s Republic of China

    Tao Wang, Qiwen Wang, Ruilong Song, Yajing Zhang, Kangbao Zhang, Yan Yuan, Jianchun Bian, Xuezhong Liu, Jianhong Gu & Zongping Liu

  3. Bijie Pilot Area Research Institute of Bijie University, Bijie, 551700, People’s Republic of China

    Qiwen Wang

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  1. Tao Wang
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Correspondence to Zongping Liu.

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Wang, T., Wang, Q., Song, R. et al. Autophagy Plays a Cytoprotective Role During Cadmium-Induced Oxidative Damage in Primary Neuronal Cultures. Biol Trace Elem Res 168, 481–489 (2015). https://doi.org/10.1007/s12011-015-0390-8

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