Role of autophagy in methylmercury-induced neurotoxicity in rat primary astrocytes

Fang Yuntao, Guo Chenjia, Zhang Panpan, Zhao Wenjun, Wang Suhua, Xing Guangwei, Shi Haifeng, Lu Jian, Peng Wanxin, Feng Yun, Jiyang Cai, Michael Aschner, Lu Rongzhu

Research output: Contribution to journalArticle

22 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)333-345
Number of pages13
JournalArchives of Toxicology
Volume90
Issue number2
DOIs
StatePublished - Feb 1 2016

Keywords

  • Antioxidants
  • Astrocytes
  • Autophagy
  • Methylmercury
  • Neuroprotection
  • Neurotoxicity

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis

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  • Cite this

    Yuntao, F., Chenjia, G., Panpan, Z., Wenjun, Z., Suhua, W., Guangwei, X., Haifeng, S., Jian, L., Wanxin, P., Yun, F., Cai, J., Aschner, M., & Rongzhu, L. (2016). Role of autophagy in methylmercury-induced neurotoxicity in rat primary astrocytes. Archives of Toxicology, 90(2), 333-345. https://doi.org/10.1007/s00204-014-1425-1