Involvement of the proteasome in the programmed cell death of NGF-deprived sympathetic neurons.

摘要: Sympathetic neurons undergo programmed cell death (PCD) upon deprivation of nerve growth factor (NGF). PCD is blocked by inhibitors the interleukin-1beta converting enzyme (ICE)/Ced-3-like cysteine protease, indicating involvement this class proteases in programme. Here we demonstrate that proteolytic activities proteasome are also essential neurons. Nanomolar concentrations several inhibitors, including highly selective inhibitor lactacystin, not only prolonged survival NGF-deprived but prevented processing poly(ADP-ribose) polymerase which known to be cleaved an ICE/Ced-3 family member during PCD. These results a key regulator neuronal and that, within process, it involved upstream family. This order events was confirmed macrophages where lactacystin inhibited activation precursor ICE subsequent generation active interleukin-1beta.