Abstract
Murine N9 microglia accumulated A beta from media containing 0.67 microM A beta within 6 h. In N9 and in primary rat microglia, chloroquine, which disrupts lysosomal pH, increased A beta-induced accumulation of A beta, particularly A beta1-42. Leupeptin similarly enhanced A beta accumulation. The scavenger receptor antagonist fucoidan did not affect acute chloroquine-dependent A beta1-42 accumulation, demonstrating uptake of non-aggregated A beta. After prolonged incubations, chloroquine enhanced A beta multimer (8-12 kDa) accumulation, an effect inhibited by fucoidan. Disruptions of the lysosomal system enhance A beta and its multimer formation. Despite negligible effects of fucoidan on initial A beta uptake, chronic exposure inhibits multimer accumulation, demonstrating a role for scavenger receptor in multimer accumulation.
Publication types
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amyloid beta-Peptides / pharmacokinetics*
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Animals
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Biological Transport / drug effects
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Cell Line
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Cells, Cultured
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Chloroquine / pharmacology*
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Kinetics
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Leupeptins / pharmacology*
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Membrane Proteins*
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Mice
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Microglia / cytology
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Microglia / drug effects
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Microglia / metabolism*
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Peptide Fragments / pharmacokinetics*
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Polysaccharides / pharmacology
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Rats
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Receptors, Immunologic / antagonists & inhibitors
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Receptors, Lipoprotein*
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Receptors, Scavenger
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Scavenger Receptors, Class B
Substances
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Amyloid beta-Peptides
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Leupeptins
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Membrane Proteins
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Peptide Fragments
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Polysaccharides
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Receptors, Immunologic
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Receptors, Lipoprotein
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Receptors, Scavenger
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Scarb1 protein, mouse
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Scavenger Receptors, Class B
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amyloid beta-protein (1-42)
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Chloroquine
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fucoidan
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leupeptin