Cutting edge Seminar
Speaker: Yoshito Kumagai (Professor, Laboratory of Environmental Biology Graduate School of Life and Environmental Sciences, the University of Tsukuba)
Title: Chemical Biology of Methylmercury
Date&Time: 1 Feb. (Wed.) 2017, 12:00- 13:00
Venue: Conference Room(1F), IMEG
Abstract:
Methylmercury (MeHg) is strongly accumulated by fish and marine mammals, and is found at the highest concentrations in large predatory species at the top of the aquatic food chain. The compound was identified as the causative agent of “Minamata disease”, based deaths in Minamata City on the Japanese island of Kyushu. This environmental electrophile reacts covalently with cellular protein thiols because of its high affinity for nucleophilic groups. Although MeHg-mediated S-mercuration of cellular proteins is believed to be involved in the toxicological effects of MeHg, Some MeHg, however, binds to glutathione produced by glutamate-cysteine ligase (GCL) to form a MeHg-SG adduct that is transported into the extracellular space by multidrug resistance-associated proteins (MRPs). Of interest, transcription factor Nrf2 cooperatively regulates gene expression of GCL and MRP. On the other hand, cysteine persulfide (CysSSH) produced by cystathionine g-lyase (CSE) is highly reactive nucleophiles that are able to react with electrophiles such as MeHg. In the lecture, I will introduce that Nrf2 and CSE play a critical role in repression of MeHg toxicity in vitro and in vivo through facilitation of detoxification/excretion of MeHg and capture of MeHg associated with inactivation of the environmental electrophile, respectively.
Reference:
Environmental electrophiles: protein adducts, modulation of redox signaling and interaction with persulfides/polysulfides. Chem Res Toxicol in press, 2017.
Methylmercury, an environmental electrophile capable of activation and disruption of the Akt/CREB/Bcl-2 signal transduction pathway in SH-SY5Y cells. Sci Rep 6: 28944, 2016.
Involvement of reactive persulfides in biological bismethylmercury sulfide formation. Chem Res Toxicol 28: 1301-1306, 2015.
Isothiocyanates reduce mercury accumulation via an Nrf2-dependent mechanism during exposure of mice to methylmercury. Environ Health Perspect 119: 1117-1122, 2011.
