BREFELDIN A-INDUCED APOPTOSIS IS EXPRESSED IN RAT NEURONS WITH DEPHOSPHORYLATED TAU-PROTEIN

Brefeldin A (BFA) is a fungus metabolite (penicillum brefeldanum) that is known to produce the disintegration of the Golgi apparatus in expo sed cells, and apoptosis in various cancer cells. This study reports t hat in rat primary cortical cell cultures BFA also produces apoptosis assessed by the TUNEL method and DAPI (4',6-diemidino-2-phenylindole) staining. The percentages of apoptotic neurons range from 26.9% +/- 8. 3 to 43.2 +/- 2.5% in cultures exposed from 4 to 8 h to BFA (10 mu g/m l). A double fluorescent staining, using AT8 antibody (phosphorylated tau) or tau1 antibody (dephosphorylated tau) associated with DAPI labe ling reveals that tau1 positive neurons are more sensitive to BFA-indu ced apoptosis compared to AT8 positive neurons. This result and previo us results using other apoptosis inducers suggest that tau phosphoryla tion in the vicinity of the AT8-tau1 epitopes is a marker of resistanc e or sensitivity to neuronal apoptosis in rat cortical cell cultures. (C) 1998 Published by Elsevier Science Ireland Ltd. All rights reserve d.