Atg5-dependent autophagy plays a protective role against methylmercury-induced cytotoxicity. (16th November 2016)

• Record Type: Journal Article
• Authors: Takanezawa, Yasukazu; Nakamura, Ryosuke; Sone, Yuka; Uraguchi, Shimpei; Kiyono, Masako
• Is Part Of: Toxicology letters. Volume 262(2016)
• Page Start: 135
• Page End: 141
• Publication Date: 2016-11-16
• Subjects: Methylmercury -- Autophagy -- LC3 -- p62 -- Atg5; Toxicology -- Periodicals; 363.179
• DOI: 10.1016/j.toxlet.2016.09.007
• Languages: English
• ISSNs: 0378-4274

Abstract

Graphical abstract: 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.