Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
4325994 | Brain Research | 2011 | 10 Pages |
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.