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 vascula r form of beta-amyloid 1-40 (beta-AP). PC12 cells treated with beta-AP show ed time- and concentration-dependent lysosomal system activation and cell t oxicity. We observed increases in the number and size of cytoplasmic lysoso mes as indicated by increased acid phosphatase reactivity. Some lysosomes w ere in the form of multivesicular bodies or large residual bodies that appe ared to arise by autophagia or by endocytotic uptake. Double-sided plasma m embrane 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) p opulation in the plasma membrane P-face showed that both control and beta-A P treated cells had two major P-face IMP populations, small-diameter (4-8 n m) IMPs, and large-diameter (greater than or equal to 9nm) IMPs. The larger category of IMPs was found to possess a greater average diameter in the be ta-AP treated cells than in the control cells. These IMPs could represent m odifications to existing transmembranous receptors, channels, or transducin g molecules by the beta-AP. These results demonstrate that beta-AP can indu ce time- and concentration-dependent ultrastructural changes in PC12 cell m embranes.