The selenium (Se)-containing antioxidant selenoneine (2-selenyl-Nα,Nα,Nα-trimethyl-l-histidine) has recently been discovered to be the predominant form of organic Se in tuna blood. Although dietary intake of fish Se has been suggested to reduce methylmercury (MeHg) toxicity, the molecular mechanism of MeHg detoxification by Se has not yet been determined. Here, we report evidence that selenoneine accelerates the excretion and demethylation of MeHg, mediated by a selenoneine-specific transporter, organic cations/carnitine transporter-1 (OCTN1). Selenoneine was incorporated into human embryonic kidney HEK293 cells transiently overexpressing OCTN1 and zebrafish blood cells by OCTN1. The Km for selenoneine uptake was 13.0 μM in OCTN1-overexpressing HEK293 cells and 9.5 μM in zebrafish blood cells, indicating high affinity of OCTN1 for selenoneine in human and zebrafish cells. When such OCTN1-expressing cells and embryos were exposed to MeHg–cysteine (MeHgCys), MeHg accumulation was decreased and the excretion and demethylation of MeHg were enhanced by selenoneine. In addition, exosomal secretion vesicles were detected in the culture water of embryos that had been microinjected with MeHgCys, suggesting that these may be responsible for MeHg excretion and demethylation. In contrast, OCTN1-deficient embryos accumulated MeHg, and MeHg excretion and demethylation were decreased. Furthermore, Hg accumulation was decreased in OCTN1-overexpressing HEK293 cells, but not in mock vector-transfected cells, indicating that selenoneine and OCTN1 can regulate MeHg detoxification in human cells. Thus, the selenoneine-mediated OCTN1 system regulates secretory lysosomal vesicle formation and MeHg demethylation.Electronic supplementary materialThe online version of this article (doi:10.1007/s10126-013-9508-1) contains supplementary material, which is available to authorized users.

Levels of the selenium-containing imidazole compound selenoneine and overall organic selenium were measured in the muscle of fishes by speciation analysis.

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Nucleotide sequences in internal transcribed spacer (ITS)-1 region derived from dried nori products produced in Japan, China, and the Republic of Korea were compared. Thalli contained in the Japanese products were genetically homogenous, and their nucleotide sequences in ITS-1 were identical to those of the reference strains of Pyropia yezoensis f. narawaensis. In Chinese products, the thalli were related to P. yezoensis strain Minomiasakusa. In contrast, the thalli in the Korean products were genetically heterogeneous, and several different P. yezoensis strains and other Pyropia spp. were used for dried nori products. In some thalli produced in both China and Korea, the DNA sequences of the ITS-1 region were identical with that of Japan, suggesting that the cultivar strains might have been transplanted from Japan to China in recent years. The 432-bp-long nucleotide sequences in the ITS-1 region of thalli derived from Japanese origin were cleaved to two restriction fragments at 154 and 278 bp by cleavage of PCR-amplified products using MspI. Conversely, almost all of the corresponding sequences derived from China and Korea were lacking MspI or other restriction patterns, except for nori products from some areas that cultivate a closely related strain to the Japanese cultivar.