Protection against amyloid beta cytotoxicity by sulforaphane: Role of the proteasome
The 26S proteasome plays a major role in degradation of abnormal proteins within the cell. The indirect antioxidant including sulforaphane (SFN) protects cells from oxidative damage by increasing the expression of Nrf2-target genes. It has been observed that the expression of multiple subunits of the proteasome was up-regulated by indirect antioxidants through the Nrf2 pathway. In the current study, the role of SFN in amyloid β1–42 (Aβ1–42)-induced cytotoxicity has been investigated in murine neuroblastoma cells. Treatment with SFN protected cells from Aβ1–42-mediated cell death in Neuro2A and N1E 115 cells. Inhibition of proteasome activities by MG132 could abolish the protective effect of SFN against Aβ1–42. Neuro2A cells, which were stably overexpressing the catalytic subunit of the proteasome PSMB5, showed an elevated resistance toward Aβ1–42 toxicity compared to control cells. Furthermore, the in vitro assay demonstrated that the Aβ1–42 peptide is degraded by the proteasome fraction. These results suggest that proteasome-inducing indirect antioxidants may facilitate the removal of the Aβ1–42 peptide and lead to the amelioration of abnormal protein-associated etiologies.
Key words26S proteasome Indirect antioxidant Sulforaphane Amyloid beta Protein aggregation
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