In Vivo Formation of HgSe Nanoparticles and Hg–Tetraselenolate Complex from Methylmercury in SeabirdsImplications for the Hg–Se Antagonism

• Main Authors: Alain Manceau (1455781), Anne-Claire Gaillot (1549156), Pieter Glatzel (1296600), Yves Cherel (213795), Paco Bustamante (288199)
• Format: Other Non-Article Part of Journal/Newspaper
• Language: unknown
• Published: 2021
• Subjects: Biochemistry; Genetics; Molecular Biology; Pharmacology; Cancer; Environmental Sciences not elsewhere classified; Biological Sciences not elsewhere classified; Chemical Sciences not elsewhere classified; Physical Sciences not elsewhere classified; giant petrels Macronectes spp; 12 Sec residues; form multinuclear Hg x; HgSe; energy-resolution X-ray absorption; transmission electron microscopy; bioavailable Se; Giant Petrels
• Online Access: https://doi.org/10.1021/acs.est.0c06269.s001

In vivo and in vitro evidence for detoxification of methylmercury (MeHg) as insoluble mercury selenide (HgSe) underlies the central paradigm that mercury exposure is not or little hazardous when tissue Se is in molar excess (Se:Hg > 1). However, this hypothesis overlooks the binding of Hg to selenoproteins, which lowers the amount of bioavailable Se that acts as a detoxification reservoir for MeHg, thereby underestimating the toxicity of mercury. This question was addressed by determining the chemical forms of Hg in various tissues of giant petrels Macronectes spp. using a combination of high energy-resolution X-ray absorption near edge structure and extended X-ray absorption fine structure spectroscopy, and transmission electron microscopy coupled to elemental mapping. Three main Hg species were identified, a MeHg-cysteinate complex, a four-coordinate selenocysteinate complex (Hg­(Sec) 4 ), and a HgSe precipitate, together with a minor dicysteinate complex Hg­(Cys) 2 . The amount of HgSe decreases in the order liver > kidneys > brain = muscle, and the amount of Hg­(Sec) 4 in the order muscle > kidneys > brain > liver. On the basis of biochemical considerations and structural modeling, we hypothesize that Hg­(Sec) 4 is bound to the carboxy-terminus domain of selenoprotein P (SelP) which contains 12 Sec residues. Structural flexibility allows SelP to form multinuclear Hg x (Se,Sec) y complexes, which can be biomineralized to HgSe by protein self-assembly. Because Hg­(Sec) 4 has a Se:Hg molar ratio of 4:1, this species severely depletes the stock of bioavailable Se for selenoprotein synthesis and activity to one μg Se/g dry wet in the muscle of several birds. This concentration is still relatively high because selenium is naturally abundant in seawater, therefore it probably does not fall below the metabolic need for essential selenium. However, this study shows that this may not be the case for terrestrial animals, and that muscle may be the first tissue potentially injured by Hg toxicity.