Fig. 1.

Secretion of APP-α in human fibroblasts. Bryostatin (Bry, 0.1 nM, solid bar) dramatically enhanced the amount of sAPP-α in the medium after 3 h of incubation in a well characterized autopsy confirmed AD cell line (P < 0.0001, ANOVA). The graph units are relative to the vehicle, DMSO, alone (1). Bryostatin was significantly (P < 0.001, Tukey's posttest) more potent than another PKC activator, BL, at the same concentration (0.1 nM). Pretreatment (rightmost bar) with staurosporin (Sta, 100 nM) completely abolished the effect of bryostatin (0.1 nM). Bryostatin was also effective in enhancing secretion in two control cell lines, although to a lesser extend than in the AD cell line (hatched bar). A time course (for the AD cell line) is depicted in Inset. Secretion is clearly near enhanced by 15 min of incubation [bryostatin (Bryo), 0.1 nM] and near maximal at 160 min of incubation, remaining elevated up to 3 h. Bryostatin at a lower concentration, 0.01 nM, was much slower but had about the same effect on secretion after 120 min of incubation.