抄録
System B0 is a sodium dependent transporter that transports wide variety of neutral amino acids in the intestinal and renal proximal tubular epithelial cells. Methylmercury (MeHg) readily and non-enzymatically reacts with cysteine to form conjugate structurally similar to methionine. In this study, we investigated the molecular mechanisms of absorptive transport of MeHg in intestine using Xenopus oocytes expressing B0AT1. Uptake of [14C]L-leucine by B0AT1 was inhibited by MeHg-Cys conjugate, Leu, Cys, Met and Phe in concetration-dependent manner. The IC50 of MeHg-Cys conjugate was significantly lower than that of Leu, Cys, Met and Phe, indicating that B0AT1 is a high affinity MeHg transporter. To assess MeHg-Cys conjugate transport, we measured [14C]MeHg uptake in Xenopus oocytes expressing B0AT1 in the presence or absence of sodium. The [14C]MeHg was transported only in the presence of cysteine and the transport was significantly sodium dependent and inhibited by a system B0 inhibitor BCH. Our current findings indicate that B0AT1 absorb MeHg in the form of cysteine conjugate from the intestinal lumen across the brush-border membrane into the cells and is supposed to be plays a critical role in the pathogenesis of Minamata disease.
