Transport of Methylmercury through the Epithelial Type Amino Acid Transporter System B0

Authors

  • Rafiqul Islam Assistant Professor, Department of Pharmacology, National Institute of Neurosciences & Hospital, Dhaka, Bangladesh
  • Naohiko Anzai Professor, Department of Pharmacology, Kyorin University School of Medicine, Tokyo, Japan
  • Nesar Ahmed Medical Officer, Department of Medicine, MAG Osmani Medical College, Sylhet, Bangladesh
  • Mohammad Ahtashamul Haque Assistant Professor, Department of Oral and Maxillo-Facial Surgery, Dhaka Medical College, Dhaka, Bangladesh
  • Shamima Ferdous PhD in Agriculture, Bangladesh Agriculture University, Mymensingh , Bangladesh
  • Sagir Ahmed Consultant (Medicine), Department of Neurology, National Institute of Neurosciences & Hospital, Dhaka, Bangladesh
  • MS Jahirul Haque Chowdhury Professor, Department of Clinical Neurology, National Institute of Neurosciences & Hospital, Dhaka, Bangladesh
  • Md Tauhidul Islam Chowdhury Associate Professor, Department of Neurology, National Institute of Neurosciences & Hospital, Dhaka, Bangladesh
  • Wahida Begum Associate Professor, Department of Neuroradiology & Imaging, National Institute of Neurosciences & Hospital, Dhaka, Bangladesh
  • Mohammad Akter Hossain Assistant professor, Department of Neurology, National Institute of Neurosciences & Hospital, Dhaka, Bangladesh
  • Farhana Moslehuddin Consultant Physician, Stroke & Neurology, East Sussex NHS, UK
  • KM Nazmul Islam Joy Junior Consultan, Medicine, Sarkari Kormochari Hospital, Dhaka, Bangladesh
  • Yoshikatsu Kanai Professor, Department of Pharmacology, Kyorin University School of Medicine, Tokyo, Japan
  • Hitoshi Endou Professor, Department of Pharmacology, Kyorin University School of Medicine, Tokyo, Japan

DOI:

https://doi.org/10.3329/jninb.v5i2.43017

Keywords:

Amino acids transport; Methionine; Methyl-mercury-Cysteine conjugate

Abstract

Background: 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 the amino acid methionine.

Objective: In this study, we investigated the molecular mechanism of absorptive transport of MeHg in intestine using Xenopus oocytes expressing hB0AT1 and the uptake of metylmercry-Cys (MeHg-Cys) by heterodimeric amino acids transporter.

Methodology: We confirmed the uptake of [14C] L-Leucine a potent substrate for the hB0AT1 amino acids transporter. The uptake of [14C] L-leucine by hB0AT1 was inhibited by MeHg-Cys conjugate, leucine, cysteine, methinine and phenylalanine in concentration–dependent manner. The IC50 of MeHg-Cys conjugate was significantly lower than that of leucine, cysteine, methinine and phenylalanine, indicating that hB0AT1 is a high affinity MeHg transporter. To assess MeHg-Cys conjugate transport, we measured [14C] MeHg uptake in Xenopus oocytes expressing hB0AT1 in presence or absence of sodium. The [14C] MeHg was transport only in the presence of cysteine and the transport was significantly sodium dependent and inhibited by a system B0 inhibitor 2-aminobicyclo-[2,21]- haptane-2-carboxylic acid (BCH).

Result: The current findings indicate that hB0AT1 and heterodimeric amino acids absorb MeHg in the form of cysteine conjugate from the intestinal lumen across the brush-border membrane in to the cells and is supposed to be plays a critical role in the pathogenesis of Minamata disease and present results descried a major molecular mechanism by which MeHg is transported across cell membranes and indicate that metal complexes may form a novel class of substrates for amino acid carriers.

Conclusion: In this experiment the results also suggest that uptake of Methionine and MeHg-Cys by heterodimeric amino acid transporter is significantly correlated where the uptake of Methionine and MeHg-Cys between heterodimeric amino acid transporter and hB0AT1 is not correlated.

Journal of National Institute of Neurosciences Bangladesh, 2019;5(2): 127-136

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Published

2019-09-07

How to Cite

Islam, R., Anzai, N., Ahmed, N., Haque, M. A., Ferdous, S., Ahmed, S., … Endou, H. (2019). Transport of Methylmercury through the Epithelial Type Amino Acid Transporter System B0. Journal of National Institute of Neurosciences Bangladesh, 5(2), 127–136. https://doi.org/10.3329/jninb.v5i2.43017

Issue

Vol. 5 No. 2 (2019)

Section

Original Research Articles

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