17β-estradiol (βE2) protects human retinal Muller cell against oxidative stress in vitro:: Evaluation of its effects on gene expression by cDNA microarray
17β-estradiol (βE2) protects human retinal Muller cell against oxidative stress in vitro:: Evaluation of its effects on gene expression by cDNA microarray
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作者：
Li, C;Tang, YH;Cao, W
17 β -雌二醇（β E-2）是一种有效的神经保护剂，可防止过氧化氢（H2O2）诱导的视网膜神经元细胞死亡和光诱导的光感受器变性。Muller细胞是支持视网膜神经元存活、信息处理和清除代谢废物的主要大胶质细胞。然而，β E-2在人类Muller细胞中的作用尚不清楚。本研究考察了β E-2对人Muller细胞存活和基因表达的影响。我们的数据显示β E-2能够通过抑制细胞凋亡来提高H2O2暴露后人Muller细胞的活力。微阵列分析显示，在β E-2处理后6小时，培养的人Muller细胞中69个基因（共筛选了21,324个基因）的表达发生了显著变化。4个β e -2应答基因[血栓反应蛋白1 （TSPI）、丝裂原活化蛋白激酶激酶3 （MAP3K3）、大电导钙活化钾通道β 2亚基（KCNMB2）和SRY（性别决定区Y）-box 11 (SOX11)]通过实时定量RT-PCR和半定量RT-PCR验证。有趣的是，通过RT-PCR和实时qRT-PCR检测，暴露于β E-2的人Muller细胞增加了色素上皮衍生因子（PEDF）基因的表达。我们的数据首次证明β E-2通过抑制细胞凋亡来保护培养的人Muller细胞免受h2o2诱导的细胞死亡。这种保护作用可能通过TSP1、MAP3K3、SOX11、TSP1和PEDF等基因的调控而起作用，并可能反过来在保护视网膜神经元中发挥重要作用。(c) 2005 Wiley-Liss, Inc。
17 beta-estradiol (beta E-2) is an effective neuroprotectant against hydrogen peroxide (H2O2)-induced retinal neuronal cell death and light-induced photoreceptor degeneration. Muller cells are the principal macroglia responsible for supporting retinal neuronal survival, information processing and removing metabolic waste. However, the role of beta E-2 on human Muller cells is unclear. In this study, the effects of beta E-2 on human Muller cell survival and gene expression were examined. Our data revealed that beta E-2 is able to increase human Muller cell viability after exposure to H2O2 through inhibition of apoptosis. Microarray analysis revealed significant changes in the expression of 69 genes (total of 21,324 genes screened) in cultured human Muller cells 6 h after beta E-2 treatment. Four of the beta E-2-responsive genes [thrombospondin 1 (TSPI), mitogen-activated protein kinase kinase kinase 3 (MAP3K3), large conductance calcium-activated potassium channel beta 2 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 Muller cells to beta E-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 beta E-2 protects cultured human Muller cells against H2O2-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. (c) 2005 Wiley-Liss, Inc.