Modulation of APP processing and secretion by okadaic acid in primary guinea pig neurons

Primary cultures of guinea pig neurons were used as a model system to study the influence of the protein phosphatase inhibitor okadaic acid (OA) on the secretion, processing and phosphorylation of the amyloid precursor protein (APP). This primary cell culture system mimics more closely than other cell culture systems the human in vivo condition, as guinea pig APP is 98% homologous to human APP at the protein level, identical regarding the Abeta sequence and is processed in a similar manner as human APP. Both intracellular and secreted APP was upregulated by OA treatment (0.3 nM-10 nM) of 14 days old cultures in a concentration dependent manner while the amount of Abeta in the medium was decreased. OA treatment did not affect cell membrane integrity of primary neurons but induced DNA fragmentation. Phosphorylation of APP was unchanged by the low OA concentration used. These results show that OA treatment of guinea pig primary cultures might be used as a model to study the effects of modulation of signal transduction on secretion and processing of APP.