17beta-estradiol (betaE2) protects human retinal Müller cell against oxidative stress in vitro: evaluation of its effects on gene expression by cDNA microarray.
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.
Li
Chao
C
Department of Ophthalmology, University of Oklahoma Health Science Center, Dean A. McGee Eye Institute, 608 Stanton L. Young Blvd, Oklahoma City, 73104, USA.
Tang
Yuhong
Y
Li
Feng
F
Turner
Sean
S
Li
Kong
K
Zhou
Xiaohong
X
Centola
Michael
M
Yan
Xiaorong
X
Cao
Wei
W
D000975:Antioxidants; D017209:Apoptosis / Q000187:drug effects; D002478:Cells, Cultured; D004958:Estradiol / Q000494:pharmacology*; D005434:Flow Cytometry; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors / Q000633:toxicity; D020411:Oligonucleotide Array Sequence Analysis; D016877:Oxidants / Q000633:toxicity; D018384:Oxidative Stress / Q000187:drug effects*; D010857:Pigment Epithelium of Eye / Q000378:metabolism; D012160:Retina / Q000166:cytology* / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013778:Tetrazolium Salts; D013844:Thiazoles
D000975:Antioxidants; D016877:Oxidants; D013778:Tetrazolium Salts; D013844:Thiazoles; D004958:Estradiol; D006861:Hydrogen Peroxide; C022616:thiazolyl blue