Involvement of a Na+-coupled Oligopeptide Transport System for β-amyloid Peptide (Aβ1–42) in Brain Cells

Kei Higuchi, Toshihiro Sato, Yangzom D. Bhutia, Vadivel Ganapathy

Research output: Contribution to journalArticle

Abstract

Purpose: A Na+-coupled transport system in mammalian cells is responsible for the uptake of oligopeptides consisting of 5 or more amino acids. Here we investigated if this transport system is expressed in brain cells and transports the 42-amino-acid β-amyloid peptide (Aβ1–42). Methods: The human and mouse neuronal cell lines SK-N-SH and HT22, human microglial cell line HMC-3, and human blood-brain barrier endothelial cell line hCMEC/D3 were used to monitor the uptake of [3H]-deltorphin II (a heptapeptide) and fluorescence-labeled Aβ1–42. Results: All four cell lines exhibited Na+-coupled uptake of deltorphin II. Aβ1–42 competed with deltorphin II for the uptake. Uptake of fluorescence-labeled Aβ1–42 was detectable in these cell lines, and the uptake was Na+-dependent and inhibitable by deltorphin II. The Na+-coupled uptake disappeared at high concentrations of Aβ1–42 due to oligomerization of the peptide. Exposure of the cells to excess iron abolished the uptake. In hCMEC/D3 cells cultured on Transwell filters, the uptake was localized preferentially to the abluminal membrane. Conclusion: A Na+-coupled transport system mediates the uptake of Aβ1–42 monomers in neuronal and microglial cells. The same system is also responsible for the uptake of Aβ1–42 from brain into blood-brain barrier endothelial cells. These findings have relevance to Alzheimer’s disease.

Original languageEnglish
Article number98
JournalPharmaceutical research
Volume37
Issue number6
DOIs
Publication statusPublished - 2020 Jun 1

Keywords

  • Oligopeptide transport system
  • blood-brain barrier
  • deltorphin II
  • neuronal and microglial cells
  • β-amyloid peptide

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry
  • Pharmacology (medical)

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