Abstract:
: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.
journal_name
Gliajournal_title
Gliaauthors
Li C,Tang Y,Li F,Turner S,Li K,Zhou X,Centola M,Yan X,Cao Wdoi
10.1002/glia.20291subject
Has Abstractpub_date
2006-03-01 00:00:00pages
392-400issue
4eissn
0894-1491issn
1098-1136journal_volume
53pub_type
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