Role of MAPK in ceramide-induced cell death in primary cultured astrocytes from mouse embryonic brain.

Ceramide has been suggested to be involved in a variety of cell signaling pathways including mitogen-activated protein kinases. The present study was undertaken to examine whether mitogen-activated protein kinases are involved in ceramide-induced cell death in primary cultured astrocytes isolated from mouse embryonic brain. Ceramide induced apoptotic death in a dose- and time-dependent manner. Ceramide-induced cell death was dependent on generation of reactive oxygen species. Ceramide caused activation of extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK). Pharmacological inhibitors of these kinases prevented ceramide-induced cell death. Ceramide induced an increase in Bax expression, depolarization of mitochondrial membrane potential, and caspase activation. Such effects were inhibited by ERK and JNK inhibitors. These results suggest that activation of ERK and JNK is involved in ceramide-induced apoptosis through a mitochondria-dependent pathway in astrocytes.