Repression of mercury accumulation and adverse effects of methylmercury exposure is mediated by cystathionine γ-lyase to produce reactive sulfur species in mouse brain. (15th September 2020)

• Record Type: Journal Article
• Authors: Akiyama, Masahiro; Unoki, Takamitsu; Yoshida, Eiko; Ding, Yunjie; Yamakawa, Hiroto; Shinkai, Yasuhiro; Ishii, Isao; Kumagai, Yoshito
• Is Part Of: Toxicology letters. Volume 330(2020)
• Page Start: 128
• Page End: 133
• Publication Date: 2020-09-15
• Subjects: CSE cystathionine γ-lyase -- CySSH cysteine persulfide -- GSSH glutathione persulide -- H2S hydrogen sulfide -- MeHg methylmercury -- (MeHg)2S bismethylmercury sulfide -- Nrf2 NF-E2-related factor 2 -- RSS reactive sulfur species; Reactive sulfur species -- Sulfur adduct -- Cystathionine γ-lyase -- Methylmercury; Toxicology -- Periodicals; 363.179
• DOI: 10.1016/j.toxlet.2020.05.007
• Languages: English
• ISSNs: 0378-4274

Abstract

Highlights: Cerebella that lacked CSE are susceptible to MeHg. CSE deletion facilitates Hg accumulation in the brain. Polysulfide suppresses the accumulation of Hg in the brain of mice caused by CSE deficiency. Abstract: Reactive sulfur species (RSS), such as hydropersulfides and hydropolysulfides with high nucleophilicity, contain mobilized sulfur that readily captures xenobiotic electrophiles, leading to their sulfur adducts. We have previously reported that RSS produced by cystathionine γ-lyase (CSE) captures the electrophilic metal methylmercury (MeHg) to form inert sulfur adducts, which in turn play a critical role in the protection against MeHg-induced motor impairment in mice. However, the mechanism underlying this neuroprotective effect is not fully understood. Here, we addressed this using CSE-knockout mice. The cerebellum of CSE-knockout mice was more susceptible to MeHg than that of wild type mice. Moreover, these CSE-deficient mice exhibited a higher level of mercury accumulation in the brain. However, co-treatment with sodium tetrasulfide, an RSS able to capture MeHg, leading to the formation of its sulfur adducts, blocked the increased accumulation of mercury, motor dysfunction and mortality caused by CSE deficiency. Our findings suggest that capturing MeHg by RSS in association with its sulfur adduct formation is involved in the repression of the brain distribution and deleterious effects of MeHg.