Protection against amyloid beta cytotoxicity by sulforaphane: Role of the proteasome

• DOI: 10.1007/s12272-009-1124-2
• Publication Date: 2009-01-28T06:55:01Z
• Authors: Hyun-Min Park; Jung-Ae Kim; Mi-Kyoung Kwak
• Keywords: Neurons; Proteasome Endopeptidase Complex; 0303 health sciences; Amyloid beta-Peptides; Dose-Response Relationship, Drug; Cell Survival; Leupeptins; Cysteine Proteinase Inhibitors; Transfection; Antioxidants; Peptide Fragments; Mice; Neuroblastoma; 03 medical and health sciences; Cytoprotection; Isothiocyanates; Cell Line, Tumor; Sulfoxides; Animals; Promoter Regions, Genetic; Proteasome Inhibitors; Thiocyanates

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 beta(1-42) (Abeta(1-42))-induced cytotoxicity has been investigated in murine neuroblastoma cells. Treatment with SFN protected cells from Abeta(1-42)-mediated cell death in Neuro2A and N1E 115 cells. Inhibition of proteasome activities by MG132 could abolish the protective effect of SFN against Abeta(1-42). Neuro2A cells, which were stably overexpressing the catalytic subunit of the proteasome PSMB5, showed an elevated resistance toward Abeta(1-42) toxicity compared to control cells. Furthermore, the in vitro assay demonstrated that the Abeta(1-42) peptide is degraded by the proteasome fraction. These results suggest that proteasome-inducing indirect antioxidants may facilitate the removal of the Abeta(1-42) peptide and lead to the amelioration of abnormal protein-associated etiologies.