CERAMIDE INDUCES APOPTOSIS IN PC12 CELLS

The novel lipid second messenger, ceramide, induced apoptosis in PC12 cells as determined morphologically by nuclear appearance and internuc leosomal DNA fragmentation, Apoptosis was induced by exogenous C-2-cer amide in a dose- and time-dependent manner, Natural ceramide and C-6-c eramide had a similar effect, This response mas specific since the str uctural analog C-2-dihydroceramide and other related lipids failed to initiate apoptosis, The apoptotic effect of ceramide also depends crit ically on cell plating density, Furthermore, the peptide inhibitor of interleukin-1 beta converting enzyme (ICE)-like proteases, Z-VAD.FMK, completely prevented the nuclear changes induced by ceramide, implicat ing the involvement of ICE-like protease activation in ceramide-induce d apoptosis in PC12 cells.