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1.
Mar Biotechnol (NY) ; 15(5): 559-70, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-23709046

RESUMEN

The selenium (Se)-containing antioxidant selenoneine (2-selenyl-N α,N α,N α-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 K m 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.


Asunto(s)
Histidina/análogos & derivados , Inactivación Metabólica/fisiología , Compuestos de Metilmercurio/farmacocinética , Compuestos de Organoselenio/farmacología , Pez Cebra/fisiología , Animales , Elementos sin Sentido (Genética) , Western Blotting , Fluorescencia , Células HEK293 , Histidina/farmacología , Humanos , Etiquetado Corte-Fin in Situ , Larva/efectos de los fármacos , Lisosomas/metabolismo , Compuestos de Metilmercurio/toxicidad , Proteínas de Transporte de Catión Orgánico/metabolismo , Simportadores , Ultracentrifugación , Pez Cebra/metabolismo
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