Methylmercury, an environmental electrophile capable of activation and disruption of the Akt/CREB/Bcl-2 signal transduction pathway in SH-SY5Y cells

• DOI: 10.1038/srep28944
• Publication Date: 2016-06-30T09:23:17Z
• Authors: Takamitsu Unoki; Yumi Abiko; Takashi Toyama; Takashi Uehara; Koji Tsuboi; Motohiro Nishida; Toshiyuki Kaji; Yoshito Kumagai
• Keywords: SH-SY5Y; Cell Signaling

Abstract Methylmercury (MeHg) modifies cellular proteins via their thiol groups in a process referred to as “ S -mercuration”, potentially resulting modulation of the signal transduction pathway. We examined whether low-dose MeHg could affect Akt signaling involved cell survival. Exposure human neuroblastoma SH-SY5Y cells up 2 μM phosphorylated and its downstream molecule CREB, presumably due inactivation PTEN through -mercuration. As result, anti-apoptotic protein Bcl-2 was up-regulated by MeHg. The activation Akt/CREB/Bcl-2 mediated was, at least part, linked defence because either pretreatment with wortmannin block PI3K/Akt or knockdown enhanced MeHg-mediated cytotoxicity. In contrast, increasing concentrations disrupted signaling. This phenomenon attributed -mercuration CREB Cys286 rather than Akt. These results suggest that although is an apoptosis-inducing toxicant, this environmental electrophile able activate survival pathway lower prior apoptotic death.