Bisindolylmaleimide prevents cerebellar granule cells apoptosis: a possible role for PKC

Cerebellar granule cells (CGC) are amongst the most abundant neuronal cells in the mammalian central nervous system. In vitro, they undergo apoptosis when deprived of depolarizing concentrations of KCl, providing an interesting system to study neuronal apoptosis. Despite its significance, the intracellular mechanisms that follow an apoptotic insult are poorly understood. Bisindolylmaleimide, a specific protein kinase C (PKC) inhibitor, blocks cell death and apoptosis with an optimal concentration of 10 microM. Bisindolylmaleimide also blocks apoptosis up to 7 h after KCl deprivation, suggesting that it blocks a secondary process. Ro-31-8220, another PKC inhibitor, also blocks apoptosis, but it is less effective, probably due to its lack of specificity. A possible PKC role in increasing the transcription or activating protein(s) involved in neuronal apoptosis is proposed.