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., Chowdhury, M. J. H., Chowdhury, M. T. I., Begum, W., Hossain, M. A., Moslehuddin, F., Joy, K. N. I., Kanai, Y., & 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

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Original Research Articles