Department of Emergency, The People's Hospital of Guang Du District, Kunming 650200, PR China.
Mol Med Rep. 2012 Mar;5(3):847-51. doi: 10.3892/mmr.2011.731. Epub 2011 Dec 21.
Parkinson's disease (PD) is a progressive neurodegenerative disorder with selective loss of dopaminergic neurons in the substantia nigra. Evidence suggests that oxidative stress is involved in the pathogenesis of PD. Sulforaphane (SF), a naturally occurring isothiocyanate, has been shown to protect against oxidative stress by inducing the expression of various NF-E2-related factor-2 (Nrf2) responsive genes. Previous studies have shown that SF protects dopaminergic neurons against PD-related neurotoxin 6-hydroxydopamine (6-OHDA)-induced cytotoxicity. However, the molecular mechanisms by which SF protects against 6-OHDA-induced cytotoxicity are poorly elucidated. In this study, we found that pretreatment with SF significantly reduced 6-OHDA-induced caspase-3 activation and subsequent cell death. SF also increased heme oxygenase-1 (HO-1) expression, which conferred protection against 6-OHDA-induced cytotoxicity. Furthermore, SF induced the translocation of Nrf2 into the nucleus and activated PI3K/Akt, a pathway that is involved in SF-induced Nrf2 nuclear translocation, HO-1 expression and cytoprotection. These results suggest that SF inhibits 6-OHDA-induced cytotoxicity through increasing HO-1 expression in a PI3K/Akt-dependent manner.
帕金森病（PD）是一种进行性神经退行性疾病，其特征是黑质中多巴胺能神经元的选择性丧失。有证据表明，氧化应激参与了 PD 的发病机制。萝卜硫素（SF）是一种天然存在的异硫氰酸盐，通过诱导各种 NF-E2 相关因子-2（Nrf2）反应基因的表达，已被证明可以抵抗氧化应激。先前的研究表明，SF 可以保护多巴胺能神经元免受与 PD 相关的神经毒素 6-羟多巴胺（6-OHDA）诱导的细胞毒性。然而，SF 抵抗 6-OHDA 诱导的细胞毒性的分子机制尚未阐明。在这项研究中，我们发现 SF 的预处理显著降低了 6-OHDA 诱导的 caspase-3 激活和随后的细胞死亡。SF 还增加了血红素加氧酶-1（HO-1）的表达，从而对 6-OHDA 诱导的细胞毒性提供了保护。此外，SF 诱导 Nrf2 向核内易位，并激活 PI3K/Akt，该途径参与 SF 诱导的 Nrf2 核易位、HO-1 表达和细胞保护。这些结果表明，SF 通过 PI3K/Akt 依赖性方式增加 HO-1 的表达来抑制 6-OHDA 诱导的细胞毒性。
