Activation of Caspase-8 and Caspase-9 are Required for PC12 Cells Differentiation

Abstract

Nerve growth factor- (NGF) induced potent activation of caspase-8, and caspase-9 in PC12 cells in a time-dependent manner. Peptide inhibition of caspase activity led to a potent reduction in neurite outgrowth in NGF-treated cells. Although NGF treatment resulted in cell-cycle G₀/G₁ arrest as detected by FACS cell-cycle analysis, caspase inhibitors (caspase-8 and caspase-9 inhibitors) could block the G₀/G₁ arrest in PC12 cells. We demonstrated the unique caspase cascade, caspase-8, caspase-3, and caspase-9 to occur, in this order. In conclusion, present results confirm a unique role for the caspase-8 and caspase-9 mediated signal cascade in the differentiation of PC12 cells.

Keywords:

• rat pheochromocytoma cells
• nerve growth factor
• caspase-8
• caspase-9
• neurite outgrowth