Bi. Giasson et al., Activation of stress-activated protein kinases correlates with neurite outgrowth induced by protease inhibition in PC12 cells, J NEUROCHEM, 72(3), 1999, pp. 1081-1087
PC12 cells are well characterized for their ability to differentiate into n
euronal-like cells when challenged with nerve growth factor. It has been re
ported that the calpain and proteasome inhibitor N-acetyl-Leu-Leu-norleucin
al (CI) is also able to induce neurite outgrowth in PC12 cells. In this stu
dy, we report that the inhibitor of proteasomal chymotrypsin-like activity,
carbobenzoxylle-Glu-(O-tert-butyl)-Ala-Leu-aldehyde (PSI), can also induce
differentiation of PC12 cells. Induction of neurite outgrowth with PSI, CI
, or its close analogue, carbobenzoxy-leu-leu-leucinaI (MG132), was associa
ted with stress-activated protein kinase (SAPK) activation. Neurite formati
on induced by protease inhibition was independent of mitogen-activated prot
ein kinase/extracellular signal-regulated kinase, p38/reactivating kinase,
or phosphatidylinositol 3-kinase activities. The exact mechanism by which p
rotease inhibition activates SAPKs remains to be elucidated; however, our r
esults suggest that the SAPK signal transduction cascade may be an alternat
ive and/or parallel pathway in the regulation of neuronal differentiation.