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 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.
Park
Hyun-Min
HM
College of Pharmacy, Yeungnam University, Gyeongsan, 712-749, Korea.
Kim
Jung-Ae
JA
Kwak
Mi-Kyoung
MK
D016229:Amyloid beta-Peptides / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D019610:Cytoprotection; D004305:Dose-Response Relationship, Drug; D017879:Isothiocyanates; D007976:Leupeptins / Q000494:pharmacology; D051379:Mice; D009447:Neuroblastoma / Q000201:enzymology / Q000473:pathology; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D010446:Peptide Fragments / Q000378:metabolism / Q000633:toxicity*; D011401:Promoter Regions, Genetic; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000378:metabolism*; D061988:Proteasome Inhibitors; D013454:Sulfoxides; D013861:Thiocyanates / Q000494:pharmacology*; D014162:Transfection; D015854:Up-Regulation
D016229:Amyloid beta-Peptides; D000975:Antioxidants; D015853:Cysteine Proteinase Inhibitors; D017879:Isothiocyanates; D007976:Leupeptins; D010446:Peptide Fragments; D061988:Proteasome Inhibitors; D013454:Sulfoxides; D013861:Thiocyanates; C075222:amyloid beta-protein (1-42); D046988:Proteasome Endopeptidase Complex; C478802:Psmb5 protein, mouse; C061553:ATP dependent 26S protease; C016766:sulforaphane; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde