Park Hyun-Min, Kim Jung-Ae, Kwak Mi-Kyoung
College of Pharmacy, Yeungnam University, Gyeongsan, 712-749, Korea.
Arch Pharm Res. 2009 Jan;32(1):109-15. doi: 10.1007/s12272-009-1124-2. Epub 2009 Jan 29.
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.
26S蛋白酶体在细胞内异常蛋白质的降解中起主要作用。包括萝卜硫素(SFN)在内的间接抗氧化剂通过增加Nrf2靶基因的表达来保护细胞免受氧化损伤。据观察,蛋白酶体的多个亚基的表达通过间接抗氧化剂经Nrf2途径上调。在本研究中,已在小鼠神经母细胞瘤细胞中研究了SFN在β淀粉样蛋白(1-42)(Aβ(1-42))诱导的细胞毒性中的作用。用SFN处理可保护Neuro2A和N1E 115细胞免受Aβ(1-42)介导的细胞死亡。MG132对蛋白酶体活性的抑制可消除SFN对Aβ(1-42)的保护作用。与对照细胞相比,稳定过表达蛋白酶体PSMB5催化亚基的Neuro2A细胞对Aβ(1-42)毒性表现出更高的抗性。此外,体外试验表明Aβ(1-42)肽被蛋白酶体组分降解。这些结果表明,诱导蛋白酶体的间接抗氧化剂可能有助于去除Aβ(1-42)肽,并导致改善与异常蛋白质相关的病因。