Involvement of a Na+-coupled Oligopeptide Transport System for β-amyloid Peptide (Aβ1-42) in Brain Cells.
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.
['Higuchi|Kei|K|', 'Sato|Toshihiro|T|', 'Bhutia|Yangzom D|YD|', 'Ganapathy|Vadivel|V|']
D016229:Amyloid beta-Peptides D000818:Animals D001692:Biological Transport D001812:Blood-Brain Barrier D002460:Cell Line D042783:Endothelial Cells D006801:Humans D007700:Kinetics D049990:Membrane Transport Modulators D026901:Membrane Transport Proteins D051379:Mice D008954:Models, Biological D009842:Oligopeptides D010446:Peptide Fragments D012964:Sodium
Oligopeptide transport system β-amyloid peptide blood-brain barrier deltorphin II neuronal and microglial cells