Nrf2-ARE通路在人胶质母细胞瘤U251细胞凋亡调控中的作用
The involvement of Nrf2-ARE pathway in regulation of apoptosis in human glioblastoma cell U251.
作者信息
Pan Hao, Wang Handong, Zhu Lin, Wang Xiaoliang, Cong Zixiang, Sun Kangjian, Fan Youwu
机构信息
Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, China.
出版信息
Neurol Res. 2013 Jan;35(1):71-8. doi: 10.1179/1743132812Y.0000000094. Epub 2012 Sep 20.
OBJECTIVES
NF-E2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway plays anti-apoptotic role in normal tissue and tumor. But the role of Nrf2 in apoptosis in glioma is still unknown. Here, we established this experiment to elucidate how Nrf2-ARE pathway participates in apoptosis in human glioblastoma cell U251.
METHODS
Two plasmids, pEGFP-Nrf2 and Si-Nrf2, were transfected to up- or downregulate the expression of Nrf2 in U251. After transfection, the apoptosis rate, expression of heme oxygenase-1 (HO-1), Bcl-2, Bax, caspases 3, 9 and activity of caspases 3, 9 were detected.
RESULTS
After increasing expression of Nrf2, the apoptosis rate was reduced accompanied with upregulated expression of HO-1, Bcl-2/Bax, decreased expression and activity of caspases 3, 9. After decreasing expression of Nrf2, the apoptosis rate was enhanced accompanied with downregulated expression of HO-1, Bcl-2/Bax, increased expression and activity of caspases 3, 9.
DISCUSSION
Our findings suggest that Nrf2 participates in the regulation of apoptosis in U251 through HO-1 and the 'intrinsic' apoptotic pathway.
目的
核因子E2相关因子2（Nrf2）-抗氧化反应元件（ARE）通路在正常组织和肿瘤中发挥抗凋亡作用。但Nrf2在胶质瘤细胞凋亡中的作用仍不清楚。在此，我们开展本实验以阐明Nrf2-ARE通路如何参与人胶质母细胞瘤细胞U251的凋亡过程。
方法
将两种质粒，即pEGFP-Nrf2和Si-Nrf2转染至U251细胞，以上调或下调Nrf2的表达。转染后，检测细胞凋亡率、血红素加氧酶-1（HO-1）、Bcl-2、Bax、半胱天冬酶3、9的表达以及半胱天冬酶3、9的活性。
结果
Nrf2表达增加后，细胞凋亡率降低，同时HO-1、Bcl-2/Bax表达上调，半胱天冬酶3、9的表达及活性降低。Nrf2表达降低后，细胞凋亡率升高，同时HO-1、Bcl-2/Bax表达下调，半胱天冬酶3、9的表达及活性升高。
讨论
我们的研究结果表明，Nrf2通过HO-1和“内源性”凋亡途径参与U251细胞凋亡的调控。
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