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Toxicol Lett. 2016 Nov 16;262:135-141. doi: 10.1016/j.toxlet.2016.09.007. Epub 2016 Sep 22.

Atg5-dependent autophagy plays a protective role against methylmercury-induced cytotoxicity.

Author information

1
Department of Public Health and Molecular Toxicology, School of Pharmacy, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan. Electronic address: takanezaway@pharm.kitasato-u.ac.jp.
2
Department of Public Health and Molecular Toxicology, School of Pharmacy, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.

Abstract

Methylmercury (MeHg) is a widespread environmental pollutant and causes a serious hazard to health worldwide. However, molecular mechanisms underlying MeHg toxicity remain elusive. We show that MeHg reduced mouse embryonic fibroblast (MEF) viability in a dose-dependent manner. Furthermore, MeHg treatment increased levels of autophagy markers LC3-II and p62, possibly by acting on the MAPKs signaling pathway in several cell types. MeHg exposure elevated the number of LC3 puncta in stable GFP-LC3 MEFs and the number of autophagic vacuoles. The accumulation of LC3-II and p62 increased further when complementing MeHg with autophagy inhibitor, chloroquine. Moreover, we found that autophagy-related gene 5-deficient (Atg5-/-) MEFs exhibited higher sensitivity and higher levels of p62 compared to their wild-type counterparts following MeHg exposure. This suggested that p62 was upregulated at the transcription level by MeHg and degraded by Atg5-dependent autophagy. Our data demonstrate that MeHg exposure promotes autophagy, and Atg5-dependent autophagy serves to protect cells from MeHg cytotoxicity.

KEYWORDS:

Atg5; Autophagy; LC3; Methylmercury; p62

PMID:
27667695
DOI:
10.1016/j.toxlet.2016.09.007
[Indexed for MEDLINE]

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