Amyloid-beta 1-42 induced endocytosis and clusterin/apoJ protein accumulation in cultured human astrocytes.
Recent studies indicate that astrocytes may be the primary target of secreted amyloid-beta 1-42 peptides, with the neurotoxicity representing a secondary response to astrocytic stress. Our purpose was to clarify the astrocytic stress response induced by amyloid-beta peptides in human and rat astrocytes. Human amyloid-beta 1-42 peptides and fibrils induced the appearance of cytoplasmic vacuoles in normal human astrocytes (NHA) and CCFsttg1 astrocytoma cells. Vacuoles appeared 9-12h after the amyloid-beta exposure and remained present for several days. Rat primary neonatal astrocytes showed similar but less prominent vacuolar response. Human amyloid-beta peptides 1-16, 1-28, 10-20, 17-21 and 25-35 did not cause vacuole formation. Electron microscopic observations revealed large endocytic vacuoles containing fibrillar amyloid material. Stress marker analysis did not show any increase in protein levels of HSP70, HSP90, GRP78 and GRP94. However, the protein level of clusterin/apoJ, a secreted chaperone, was strongly increased both in NHA and CCFsttg1 astrocytes. Endocytic response associated with the accumulation of clusterin/apoJ protein suggests that clusterin/apoJ has a role in the clearance of amyloid-beta peptides.
Nuutinen
Tapio
T
Department of Neuroscience and Neurology, University of Kuopio, P.O. Box 1627, FIN-70211 Kuopio, Finland.
Huuskonen
Jari
J
Suuronen
Tiina
T
Ojala
Johanna
J
Miettinen
Riitta
R
Salminen
Antero
A
D016229:Amyloid beta-Peptides / Q000502:physiology*; D001253:Astrocytes / Q000378:metabolism*; D002478:Cells, Cultured; D051152:Clusterin / Q000378:metabolism*; D004705:Endocytosis / Q000502:physiology*; D000091342:Endoplasmic Reticulum Chaperone BiP; D006801:Humans; D010446:Peptide Fragments / Q000502:physiology*
D016229:Amyloid beta-Peptides; C495242:CLU protein, human; D051152:Clusterin; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)