The ultrastructural effects of beta-amyloid peptide on cultured PC12 cells: changes in cytoplasmic and intramembranous features.
The fine structural features of cultured PC12 cells were investigated after treatment for 1, 3, or 5 days with different concentrations of the vascular form of beta-amyloid 1-40 (beta-AP). PC12 cells treated with beta-AP showed time- and concentration-dependent lysosomal system activation and cell toxicity. We observed increases in the number and size of cytoplasmic lysosomes as indicated by increased acid phosphatase reactivity. Some lysosomes were in the form of multivesicular bodies or large residual bodies that appeared to arise by autophagia or by endocytotic uptake. Double-sided plasma membrane invaginations were observed to give rise to increasingly extensive intracytoplasmic vacuolization that was correlated with duration of beta-AP treatment. Freeze-fracture studies of the intramembranous particle (IMP) population in the plasma membrane P-face showed that both control and beta-AP treated cells had two major P-face IMP populations, small-diameter (4-8 nm) IMPs, and large-diameter (> or = 9 nm) IMPs. The larger category of IMPs was found to possess a greater average diameter in the beta-AP treated cells than in the control cells. These IMPs could represent modifications to existing transmembranous receptors, channels, or transducing molecules by the beta-AP. These results demonstrate that beta-AP can induce time- and concentration-dependent ultrastructural changes in PC12 cell membranes.
Lane
N J
NJ
Department of Zoology, University of Cambridge, UK.
Balbo
A
A
Fukuyama
R
R
Rapoport
S I
SI
Galdzicki
Z
Z
D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D001798:Blood Proteins / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects / Q000648:ultrastructure; D003593:Cytoplasm / Q000187:drug effects / Q000648:ultrastructure; D004305:Dose-Response Relationship, Drug; D005614:Freeze Fracturing; D007425:Intracellular Membranes / Q000187:drug effects / Q000648:ultrastructure; D008854:Microscopy, Electron; D008867:Microtomy; D009474:Neurons / Q000187:drug effects* / Q000648:ultrastructure*; D016716:PC12 Cells; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats
D016229:Amyloid beta-Peptides; D001798:Blood Proteins; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); D002118:Calcium