Cathepsin L is involved in 6-hydroxydopamine induced apoptosis of SH-SY5Y neuroblastoma cells

Our previous study reported that cathepsin L may contribute to the death of dopaminergic neurons in rodent model of Parkinson's disease (PD). In this study we detected the changes in the expression of lysosomal cathepsin L in cellular models of PD. In human neuroblastoma SH-SY5Y cells, treatment with 6-hydroxydopamine caused an increase in cathepsin L immunoreactivity in the cytoplasm and an increased production of the active form of cathepsin L. The contribution of cathepsin L to 6-OHDA-induced NF-κB activation and death of SH-SY5Y neuroblastoma cells were evaluated with an irreversible inhibitor of cathepsin L, Z-FY(t-Bu)-DMK. 6-OHDA-induced IκB-α degradation, NF-κB p65 nuclear translocation, p53 and PUMA expression were partially blocked by Z-FY(t-Bu)-DMK. In addition, Z-FY(t-Bu)- DMK modulated the Bcl-2 family levels, and suppressed caspase-3 activation. These data indicate that cathepsin L may be involved in 6-OHDA-induced apoptosis and Parkinsonian neurodegeneration.

Research Highlights
► 6-OHDA induced translocation of cathepsin L from lysosomes to the cytosol in SH-SY5Y cells.
► Cathepsin L inhibitor, Z-FY(t-Bu)-DMK partially blocked 6-OHDA-induced IκB-α degradation.
► Z-FY(t-Bu)-DMK partially blocked 6-OHDA-induced NF-κB nuclear translocation.
► 6-OHDA-induced P53 and PUMA expression were partially blocked by Z-FY(t-Bu)-DMK.
► Z-FY(t-Bu)-DMK modulated the Bcl-2 family levels, and suppressed caspase-3 activation.