Effect of chloroquine and leupeptin on intracellular accumulation of amyloid-beta (A beta) 1-42 peptide in a murine N9 microglial cell line.
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.
Chu
T
T
Department of Medicine, University of California, Los Angeles, USA.
Tran
T
T
Yang
F
F
Beech
W
W
Cole
G M
GM
Frautschy
S A
SA
D016229:Amyloid beta-Peptides / Q000493:pharmacokinetics*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002460:Cell Line; D002478:Cells, Cultured; D002738:Chloroquine / Q000494:pharmacology*; D007700:Kinetics; D007976:Leupeptins / Q000494:pharmacology*; D008565:Membrane Proteins; D051379:Mice; D017628:Microglia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010446:Peptide Fragments / Q000493:pharmacokinetics*; D011134:Polysaccharides / Q000494:pharmacology; D051381:Rats; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B
D016229:Amyloid beta-Peptides; D007976:Leupeptins; D008565:Membrane Proteins; D010446:Peptide Fragments; D011134:Polysaccharides; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; C075222:amyloid beta-protein (1-42); D002738:Chloroquine; C007789:fucoidan; C032854:leupeptin