Protection against hydrogen peroxide-induced cell death in cultured human retinal pigment epithelial cells by 17beta-estradiol: a differential gene expression profile.
It has been demonstrated that estrogen receptors are present in the retinal pigment epithelium (RPE)-choroids complex regardless of sex. This suggests that estrogen could play a functional role in the outer retina, especially the RPE. To gain further insights on the molecular mechanisms differentially activated by 17beta-estradiol (betaE2) in RPE cells, we investigated gene expression changes in response to betaE2 in cultured RPE cells using cDNA microarray technology. A total of 47 genes among 21,329 human genes are significantly altered in response to betaE2 treatment in RPE cells. Among these 47 altered genes, 34 are up-regulated and 13 are down-regulated by betaE2. The products of 34 genes have a known or suspected function. These functions belong to various categories, including caspases; extracellular matrix proteins; metabolism pathway components; GTP/GDP exchangers and G-protein GTPase activity modulators; transcription activators and repressors. Six genes which may contribute to the unique functions of the RPE cells have been validated by both quantitative real-time reverse transcription (RT)-PCR and semi-quantitative RT-PCR. In addition, we also demonstrated that betaE2 quenches H2O2-induced up-regulation of apoptosis-related protein, and protects RPE cell degeneration. These results indicate that estrogen regulates functions of RPE cells and is involved in the maintaining and survival of RPE cells during oxidative stress, and its deficiency during menopause period may be a factor contributing to the development of age-related macular degeneration in elderly women.
Yu
Xiaorui
X
Department of Ophthalmology, University of Oklahoma Health Science Center, Dean A. McGee Eye Institute, 608 Stanton L. Young Blvd, Oklahoma City, OK 73104, USA.
Tang
Yuhong
Y
Li
Feng
F
Frank
Mark Barton
MB
Huang
Hu
H
Dozmorov
Igor
I
Zhu
Yanping
Y
Centola
Michael
M
Cao
Wei
W
D017209:Apoptosis / Q000187:drug effects*; D002478:Cells, Cultured; D016000:Cluster Analysis; D004847:Epithelial Cells / Q000187:drug effects / Q000502:physiology; D004958:Estradiol / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D020411:Oligonucleotide Array Sequence Analysis; D016877:Oxidants / Q000494:pharmacology*; D010857:Pigment Epithelium of Eye / Q000166:cytology*; D011960:Receptors, Estrogen / Q000378:metabolism
D016877:Oxidants; D011960:Receptors, Estrogen; D004958:Estradiol; D006861:Hydrogen Peroxide