Expression of heme oxygenase-1 is repressed by interferon-gamma and induced by hypoxia in human retinal pigment epithelial cells.

Publisher: Blackwell Science Ltd. on behalf of the Federation of European Biochemical Societies Country of Publication: England NLM ID: 0107600 Publication Model: Print Cited Medium: Print ISSN: 0014-2956 (Print) Linking ISSN: 00142956 NLM ISO Abbreviation: Eur J Biochem Subsets: MEDLINE

Publication: -2004: Oxford, UK : Blackwell Science Ltd. on behalf of the Federation of European Biochemical Societies
Original Publication: Berlin, New York, Springer.

Cell Hypoxia* ; Gene Expression Regulation, Enzymologic*; Epithelial Cells/*metabolism ; Heme Oxygenase (Decyclizing)/*metabolism ; Interferon-gamma/*metabolism ; Pigment Epithelium of Eye/*cytology; Basic-Leucine Zipper Transcription Factors ; Cell Line ; Cycloheximide/pharmacology ; DNA-Binding Proteins/genetics ; DNA-Binding Proteins/metabolism ; Dactinomycin/pharmacology ; Epithelial Cells/cytology ; Epithelial Cells/drug effects ; Fanconi Anemia Complementation Group Proteins ; Genes, Reporter ; Heme Oxygenase (Decyclizing)/genetics ; Heme Oxygenase-1 ; Humans ; Leucine Zippers ; Membrane Proteins ; NF-E2-Related Factor 2 ; Oxidative Stress ; Promoter Regions, Genetic ; Protein Synthesis Inhibitors/pharmacology ; RNA Stability ; RNA, Messenger/metabolism ; Trans-Activators/genetics ; Trans-Activators/metabolism ; Transcription Factors/genetics ; Transcription Factors/metabolism

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-gamma 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-gamma 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.

0 (BACH1 protein, human)
0 (Basic-Leucine Zipper Transcription Factors)
0 (DNA-Binding Proteins)
0 (Fanconi Anemia Complementation Group Proteins)
0 (Membrane Proteins)
0 (NF-E2-Related Factor 2)
0 (NFE2L2 protein, human)
0 (Protein Synthesis Inhibitors)
0 (RNA, Messenger)
0 (Trans-Activators)
0 (Transcription Factors)
1CC1JFE158 (Dactinomycin)
82115-62-6 (Interferon-gamma)
98600C0908 (Cycloheximide)
EC 1.14.14.18 (HMOX1 protein, human)
EC 1.14.14.18 (Heme Oxygenase (Decyclizing))
EC 1.14.14.18 (Heme Oxygenase-1)

Date Created: 20040706 Date Completed: 20040831 Latest Revision: 20161124

20231215

10.1111/j.1432-1033.2004.04241.x

15233805