Abstract
Autophagy is an evolutionarily conserved process in which cytoplasmic proteins and organelles are degraded and recycled for reuse. There are numerous reports on the role of autophagy in cell growth and death; however, the role of autophagy in methylmercury (MeHg)-induced neurotoxicity has yet to be identified. We studied the role of autophagy in MeHg-induced neurotoxicity in astrocytes. MeHg reduced astrocytic viability in a concentration- and time-dependent manner, and induced apoptosis. Pharmacological inhibition of autophagy with 3-methyladenine or chloroquine, as well as the silencing of the autophagy-related protein 5, increased MeHg-induced cytotoxicity and the ratio of apoptotic astrocytes. Conversely, rapamycin, an autophagy inducer, along with as N-acetyl-l-cysteine, a precursor of reduced glutathione, decreased MeHg-induced toxicity and the ratio of apoptotic astrocytes. These results indicated that MeHg-induced neurotoxicity was reduced, at least in part, through the activation of autophagy. Accordingly, modulation of autophagy may offer a new avenue for attenuating MeHg-induced neurotoxicity.
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Acknowledgments
We are grateful to Professor Peter Spencer and Miss Jenny Kan at Oregon Health & Science University and Dr. Wen-Xing Ding at The University of Kansas Medical Center for critical reading, comments, and English editing of the manuscript. This work was supported in part by the Natural Science Foundation of China (Nos. 30872139, 81273124, 31100964). MA was supported in part by R01 ES07331 and ES020852 from the National Institute of Environmental Health Sciences (NIEHS).
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Yuntao, F., Chenjia, G., Panpan, Z. et al. Role of autophagy in methylmercury-induced neurotoxicity in rat primary astrocytes. Arch Toxicol 90, 333–345 (2016). https://doi.org/10.1007/s00204-014-1425-1
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DOI: https://doi.org/10.1007/s00204-014-1425-1