Expression of heme oxygenase‐1 is repressed by interferon‐γ and induced by hypoxia in human retinal pigment epithelial cells

FEBS Journal - Tập 271 Số 14 - Trang 3076-3084 - 2004
Reiko Udono‐Fujimori1, Kazuhiro Takahashi2, Kazuhisa Takeda2, Kazumichi Furuyama2, Kiriko Kaneko2, Shigeru Takahashi3, Makoto Tamai4, Shigeki Shibahara2
1Department of Molecular Biology & Applied Physiology, Tohoku University School of Medicine, Sendai, Miyagi, Japan.
2Department of Molecular Biology and Applied Physiology, Tohoku University School of Medicine, Sendai
3Laboratory of Environmental Molecular Physiology, School of Life Science, Tokyo University of Pharmacy and Life Science, Hachioji
4Department of Ophthalmology, Tohoku University School of Medicine, Sendai, Japan.

Tóm tắt

The retinal pigment epithelium (RPE) is essential for maintenance of photoreceptors and normally functions under conditions enriched with reactive oxygen species. RPE therefore expresses various defense enzymes against oxidative stress, including heme oxygenase‐1 (HO‐1). HO‐1 catalyzes heme breakdown to release iron, carbon monoxide, and biliverdin, which is reduced to bilirubin, a potent radical scavenger. HO‐1 expression is induced by various environmental factors, which has been established as a defense mechanism. To explore the hypothesis that the expression level of HO‐1 is reduced in those RPE cells under certain conditions, we analyzed the effects of interferon‐γ and hypoxia, each of which represses the expression of HO‐1 mRNA in other types of human cells. Expression levels of HO‐1 mRNA were reduced by interferon‐γ in two human RPE cell lines, D407 and ARPE‐19, which was consistently associated with the induction of mRNA for Bach1, a transcriptional repressor for the HO‐1 gene. On the other hand, HO‐1 and Bach1 mRNAs were induced by hypoxia in D407 cells but remained unchanged in ARPE‐19 cells, suggesting that Bach1 is not a sole regulator for HO‐1 expression. The hypoxia‐mediated induction of HO‐1 mRNA in D407 cells depends on gene transcription and protein synthesis, as judged by the effects of their inhibitors. The half‐life of HO‐1 mRNA did not change during hypoxia. Thus, hypoxia may increase transcription of the HO‐1 gene through a certain protein factor in RPE cells. These results indicate that RPE cells maintain retinal homeostasis by repressing or inducing the expression of HO‐1, depending on the microenvironment.

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FEBS Journal

Tập 271 Số 14

3076-3084

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