The flavonoid, eriodictyol, induces long-term protection in ARPE-19 cells through its effects on Nrf2 activation and phase 2 gene expression.
The flavonoid, eriodictyol, induces long-term protection in ARPE-19 cells through its effects on Nrf2 activation and phase 2 gene expression.
复制标题
DOI：
10.1167/iovs.08-2088
复制
发表时间：
2009-05
影响因子：
4.4
通讯作者：
Hanneken A
中科院分区：
文献类型：
--
作者：
Johnson J;Maher P;Hanneken A
Eriodictyol是一种在柑橘类水果中发现的类黄酮，是据报道保护人类RPE细胞免受氧化应激诱导的细胞死亡的最有效化合物之一。在本研究中，我们确定了圣草酚诱导的II期蛋白表达是否进一步增强了人ARPE-19细胞对氧化应激的抵抗力。我们分析了圣草酚激活Nrf 2和诱导II相蛋白、血红素加氧酶（HO-1）、NAD（P）H：醌氧化还原酶1（NQO-1）和细胞抗氧化剂谷胱甘肽（GSH）的能力。我们在过表达HO-1或NQO-1的ARPE-19细胞中进行了细胞保护试验。我们比较了短期和长期圣草酚治疗后的细胞存活率，并使用显性负性Nrf 2和HO-1特异性shRNA测试了保护机制。我们证明，圣草酚诱导核转位的Nrf 2，增强HO-1和NQO-1的表达，并增加细胞内谷胱甘肽的水平。我们表明，ARPE-19细胞，过表达HO-1或NQO-1是更耐氧化应激诱导的细胞死亡比对照细胞。我们证明，圣草酚诱导的长期保护，是显着大于其短期保护，这种效果是相关的时间与Nrf 2的激活和诱导II相酶。我们证明，这种作用可以通过使用Nrf 2的显性负性和HO-1特异性的shRNA来阻断。这些发现表明圣草酚的最大益处可能是其调节基因表达和增强多种细胞对氧化损伤的防御的能力。
Eriodictyol, a flavonoid found in citrus fruits, is among the most potent compounds reported to protect human RPE cells from oxidative stress-induced cell death. In the present study, we determined whether eriodictyol-induced phase II protein expression further enhances the resistance of human ARPE-19 cells to oxidative stress. We analyzed the ability of eriodictyol to activate Nrf2 and induce the phase II proteins, heme-oxygenase (HO-1), NAD(P)H: quinone oxidoreductase 1 (NQO-1), and the cellular antioxidant glutathione, (GSH). We performed cytoprotection assays in ARPE-19 cells that were overexpressing HO-1 or NQO-1. We compared cell survival after short-term and long-term eriodictyol treatment and tested the mechanism of protection using a dominant negative Nrf2 and an shRNA specific for HO-1. We demonstrate that eriodictyol induces the nuclear translocation of Nrf2, enhances the expression of HO-1 and NQO-1, and increases the levels of intracellular glutathione. We show that ARPE-19 cells that overexpress HO-1 or NQO-1 are more resistant to oxidative stress-induced cell death than control cells. We demonstrate that eriodictyol induces long-term protection that is significantly greater than its short-term protection, and this effect is correlated temporally with both the activation of Nrf2 and the induction of phase II enzymes. We demonstrate that this effect can be blocked with the use of a dominant negative to Nrf2 and an shRNA specific to HO-1. These findings indicate the greatest benefit from eriodictyol may be its ability to regulate gene expression and enhance multiple cellular defenses to oxidative injury.
登录
查看更多内容
影响因子：
--
作者：
Kassoff, A;Kassoff, J;Chew, EY
通讯作者：
Chew, EY
影响因子：
3.4
作者：
Matsumoto, Hitoshi;Nakamura, Yuko;Ohguro, Hiroshi
通讯作者：
Ohguro, Hiroshi
DOI：
10.1073/pnas.90.7.2965
发表时间：
1993-04-01
影响因子：
11.1
作者：
PRESTERA, T;HOLTZCLAW, WD;TALALAY, P
通讯作者：
TALALAY, P
DOI：
10.1073/pnas.82.23.8232
发表时间：
1985-01-01
影响因子：
11.1
作者：
PROCHASKA, HJ;DELONG, MJ;TALALAY, P
通讯作者：
TALALAY, P
DOI：
10.1073/pnas.261572998
发表时间：
2001-12-18
影响因子：
11.1
作者：
Gao, XQ;Dinkova-Kostova, AT;Talalay, P
通讯作者：
Talalay, P