Strong antioxidant selenoneine in tuna blood: its roles in selenium redox metabolism

Selenium‐containing imidazole compound, 2‐selenyl‐ N α , N α , N α ‐ trimethyl‐L‐histidine, “selenoneine” in tuna blood had a strong antioxidant capacity and bound to hemoglobin and myoglobin (Mb), to protect them from iron autoxidation, and reacted with radicals and methylmercury (MeHg). Cell growth of human and zebrafish cultured cells were enhanced in the presence of selenoneine at 5–100 nM, and GPx1 gene expression was induced in dose‐dependent manner. Administration of selenoneine to yellowtail fish reduced ROS and met‐Mb formation, and the meat color change in dark muscle was protected. Selenoneine was incorporated into human embryonic kidney HEK293 transiently overexpressed with organic cations/carnitine transporter‐1 (OCTN1) and zebrafish embryo cells by OCTN1. The K m value of selenoneine uptake was determined to be 13.0 μM in OCTN1‐oeverexpressed HEK293 cells and 9.5 μM in zebrafish erythrocytes, respectively, indicating that selenoneine is the most specific substrate for the OCTN1 in the 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 was enhanced by the presence of 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. Therefore, the selenoneine‐mediated OCTN1 transport system accelerates secretory extracellular lysosomal vesicle formation and thus the demethylation of MeHg.