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Graefe's Archive for Clinical and Experimental Ophthalmology
Published in: Graefe's Archive for Clinical and Experimental Ophthalmology 5/2008

01-05-2008 | Basic Science

Endoplasmic reticulum stress induced by oxidative stress in retinal pigment epithelial cells

Authors: Shikun He, Jennifer Yaung, Yeong Hoon Kim, Ernesto Barron, Stephen J. Ryan, David R. Hinton

Published in: Graefe's Archive for Clinical and Experimental Ophthalmology | Issue 5/2008

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Abstract

Background

Induction of glucose-regulated protein (GRP)-78 in the endoplasmic reticulum (ER) is a protective mechanism cells use to adapt to ER stress. We evaluated the expression of GRP-78 and its regulation by an oxidant tert-butyl hydroperoxide (tBH) in human retinal pigment epithelium (RPE) cells.

Methods

We used a carboxy-H2-DCFDA staining method to detect tBH-induced accumulation of reactive oxygen species (ROS) in RPE cells, and analyzed the expression of GRP-78 in normal human fetal and adult retinas and in cultured human RPE cells by immunohistochemistry. The effects of tBH (10–100 μM) on GRP-78 and on growth arrest and DNA damage inducible genes 153 (GADD153) protein and mRNA expression were studied using Western blot and real-time polymerase chain reaction.

Results

Sections of fetal retinas were negative for GRP-78. Adult retinas showed moderate cytoplasmic GRP-78 staining in the RPE and choroid. tBH-induced ROS accumulation in RPE cells showed partial colocalization with the ER. GRP-78 and GADD153 mRNA and protein expression in cultured RPE cells were significantly upregulated by treatment with tBH.

Conclusion

tBH increases oxidative stress, increases accumulation of ROS in the ER, and upregulates expression of GRP-78 and GADD153. This supports the connection between oxidative stress and ER stress, and suggests that GRP-78 may serve a protective role in the RPE response to oxidative stress.
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Metadata
Title
Endoplasmic reticulum stress induced by oxidative stress in retinal pigment epithelial cells
Authors
Shikun He
Jennifer Yaung
Yeong Hoon Kim
Ernesto Barron
Stephen J. Ryan
David R. Hinton
Publication date
01-05-2008
Publisher
Springer-Verlag
Published in
Graefe's Archive for Clinical and Experimental Ophthalmology / Issue 5/2008
Print ISSN: 0721-832X
Electronic ISSN: 1435-702X
DOI
https://doi.org/10.1007/s00417-008-0770-2

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