Li Chao, Tang Yuhong, Li Feng, Turner Sean, Li Kong, Zhou Xiaohong, Centola Michael, Yan Xiaorong, Cao Wei
Department of Ophthalmology, University of Oklahoma Health Science Center, Dean A. McGee Eye Institute, 608 Stanton L. Young Blvd, Oklahoma City, 73104, USA.
Glia. 2006 Mar;53(4):392-400. doi: 10.1002/glia.20291.
17beta-estradiol (betaE(2)) is an effective neuroprotectant against hydrogen peroxide (H(2)O(2))-induced retinal neuronal cell death and light-induced photoreceptor degeneration. Müller cells are the principal macroglia responsible for supporting retinal neuronal survival, information processing and removing metabolic waste. However, the role of betaE(2) on human Müller cells is unclear. In this study, the effects of betaE(2) on human Müller cell survival and gene expression were examined. Our data revealed that betaE(2) is able to increase human Müller cell viability after exposure to H(2)O(2) through inhibition of apoptosis. Microarray analysis revealed significant changes in the expression of 69 genes (total of 21,324 genes screened) in cultured human Müller cells 6 h after betaE(2) treatment. Four of the betaE(2)-responsive genes [thrombospondin 1 (TSP1), mitogen-activated protein kinase kinase kinase 3 (MAP3K3), large conductance calcium-activated potassium channel beta2 subunit (KCNMB2), and SRY (sex-determining region Y)-box 11 (SOX11)] were validated by both real-time qRT-PCR and semi-quantitative RT-PCR. Interestingly, exposure of human Müller cells to betaE(2) increased pigment epithelium-derived factor (PEDF) gene expression as measured by both RT-PCR and real time qRT-PCR. Our data demonstrate, for the first time, that betaE(2) protects cultured human Müller cells against H(2)O(2)-induced cell death through the inhibition of apoptosis. This protective effect may operate through regulation of genes, such as TSP1, MAP3K3, SOX11, TSP1, and PEDF, and may in turn exert an important role in protecting retinal neurons.
17β-雌二醇（βE₂）是一种有效的神经保护剂，可抵御过氧化氢（H₂O₂）诱导的视网膜神经细胞死亡以及光诱导的光感受器退化。 Müller细胞是主要的大胶质细胞，负责支持视网膜神经细胞存活、信息处理以及清除代谢废物。然而，βE₂对人Müller细胞的作用尚不清楚。在本研究中，检测了βE₂对人Müller细胞存活和基因表达的影响。我们的数据显示，βE₂能够在人Müller细胞暴露于H₂O₂后通过抑制凋亡来提高其活力。基因芯片分析显示，βE₂处理6小时后，培养的人Müller细胞中69个基因（共筛选21324个基因）的表达发生了显著变化。通过实时定量逆转录聚合酶链反应（qRT-PCR）和半定量逆转录聚合酶链反应（RT-PCR）验证了4个βE₂反应基因[血小板反应蛋白1（TSP1）、丝裂原活化蛋白激酶激酶激酶3（MAP3K3）、大电导钙激活钾通道β2亚基（KCNMB2）和性别决定区Y框蛋白11（SOX11）]。有趣的是，通过RT-PCR和实时qRT-PCR检测发现，人Müller细胞暴露于βE₂后色素上皮衍生因子（PEDF）基因表达增加。我们的数据首次证明，βE₂通过抑制凋亡保护培养的人Müller细胞免受H₂O₂诱导的细胞死亡。这种保护作用可能通过调节TSP1、MAP3K3、SOX11、TSP1和PEDF等基因发挥作用，进而可能在保护视网膜神经元方面发挥重要作用。
