Discovery of the strong antioxidant selenoneine in tuna and selenium redox metabolism

Abstract

A novel selenium-containing compound, selenoneine, has been isolated as the major form of organic selenium in the blood and tissues of tuna. Selenoneine harbors a selenium atom in the imidazole ring, 2-selenyl-N(α), N(α), N(α)-trimethyl-L-histidine, and is a selenium analog of ergothioneine. This selenium compound has strong antioxidant capacity and binds to heme proteins, such as hemoglobin and myoglobin, to protect them from iron auto-oxidation, and it reacts with radicals and methylmercury (MeHg). The organic cations/carnitine transporter OCTN1 transports selenoneine and MeHg, regulates Se-enhanced antioxidant activity, and decreases MeHg toxicity. Thus, the dietary intake of selenoneine, by consuming fish, might decrease the formation of reactive oxygen radicals that could oxidize nucleotides in DNA, and thereby inhibit carcinogenesis, chronic diseases, and aging.

Keywords: Antioxidant; Ergothioneine; Fish; Glutathione peroxidase; Methylmercury; Organic cations/carnitine transporter OCTN1; Selenium-containing compound; Tuna.

Figure 1

Chemical structure of ergothioneine and selenoneine. The monomeric form of the selenium compound is unstable under cold and room temperature conditions. The extracted material that contains the selenoketone of the selenium compound from the tuna tissues with acetonitrile/tetrahydrofuran (1:1 in volume) accelerates selenoxo-selenol tautomerization and formation of the oxidized dimeric form.

Figure 2

Effect of selenoneine on cell growth. A: Control; B: Selenoneine. Human umbilical vein endothelial cells (HUVECs) were cultured by supplementation with 10% calf serum in the presence of selenoneine (50 μmol/L) or its absence in MCDB131 medium at 37°C for 24 h. Cell extracts with distilled water were subjected to liquid chromatography inductively coupled plasma mass spectroscopy (LC-ICP-MS) by monitoring ⁸²Se. The arrow shows a peak of selenoneine detected in the HUVEC extract with distilled water at a retention time of 10.5 min. Thus, selenoneine was incorporated into the cells and promoted cell growth.

Figure 3

Speciation analysis of organic selenium in the various tissues of bluefin tuna by LC-ICP-MS. Selenium compounds were separated with an Ultrahydrogel 120 (7.8 mm × 250 mm, Nihon Waters, Tokyo, Japan), equilibrated with 100 mmol/L ammonium formate buffer[30]. The mobile phase was delivered at 1 mL/min isocratically, and selenium was detected using online LC-ICP-MS (ELAN DRC II, PerkinElmer, Waltham, MA, USA) monitoring ⁸²Se. GPx, selenite, selenocysteine, selenomethionine, and selenoneine were eluted at retention times of 5.4, 7.4, 7.8, 9.8, and 10.5 min, respectively, and the selenium concentration was determined using the respective compounds as standards. The arrow shows the elution of selenoneine. Selenoproteins including GPx were eluted near the void volume of the column at 5.4 min.

Figure 4

Proposed model of selenium metabolism and radical detoxification.