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 depolarizating concentrations of KCl, provi ding an interesting system to study neuronal apoptosis. Despite its si gnificance, the intracellular mechanisms that follow an apoptotic insu lt are poorly understood. Bisindolylmaleimide, a specific protein kina se C (PKC) inhibitor, blocks cell death and apoptosis with an optimal concentration of 10 mu M. Bisindolylmaleimide also blocks apoptosis up to 7 h after KCl deprivation, suggesting that it blocks a secondary p rocess. Ro-31-8220, another PKC inhibitor, also blocks apoptosis, but it is less effective, probably due to its lack of specificity. A possi ble PKC role in increasing the transcription or activating protein(s) involved in neuronal apoptosis is proposed. (C) 1998 Rapid Science Ltd .