The role of calcium and magnesium ions in uptake of beta-amyloid peptides by microglial cells.
Amyloid peptides 1-40 and 1-42 (Abeta 1-40 and Abeta 1-42) are major components of diffuse and neuritic senile plaques present in the brain of patients with Alzheimers disease. Their interaction with microglial cells was studied using a system partly mimicking these plaques, which consisted in heat-killed yeast particles coated with either Abeta 1-40 or Abeta 1-42. Using these particles, it has been shown in our laboratory that LRP is involved mainly in the elimination of Abeta 1-42-coated heat-killed yeast particles and partly in that of Abeta 1-40-coated heat-killed yeast particles by microglial cells in culture. We show here that in the presence of calcium and magnesium ions extracellular chelators, namely EDTA (for both ions) and EGTA (for calcium ions), the internalization of coated heat-killed particles was impaired. In the presence of BAPTA-AM, an intracellular chelator of calcium ions and thapsigargin, an inhibitor of the endoplasmic reticulum calcium pump, no effect was observed on the phagocytosis of Abeta 1-40-coated heat-killed yeast particles, whereas that of Abeta 1-42-coated heat-killed yeast particles was affected. These results suggest that different signaling mechanisms are involved after the internalization of Abeta 1-40 and Abeta 1-42.
Choucair
N
N
UMR 7175-LC1 Departement de Pharmacologie et Physicochimie des Interactions Cellulaires et Moleculaires, University Louis Pasteur, Illkirch Cedex, France.
Laporte
V
V
Levy
R
R
Tranchant
C
C
Gies
J-P
JP
Poindron
P
P
Lombard
Y
Y
D016229:Amyloid beta-Peptides / Q000493:pharmacokinetics*; D000818:Animals; D002118:Calcium / Q000502:physiology*; D002460:Cell Line; D004492:Edetic Acid / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D008274:Magnesium / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D017628:Microglia / Q000378:metabolism*; D010446:Peptide Fragments / Q000493:pharmacokinetics*; D010587:Phagocytosis; D015398:Signal Transduction; D015003:Yeasts / Q000276:immunology
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); D004533:Egtazic Acid; D004492:Edetic Acid; D008274:Magnesium; D002118:Calcium