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Oxygen tension regulates heme oxygenase‐1 gene expression in mammalian cell lines
Author(s) -
Takahashi Shigeru,
Takahashi Yuji,
Yoshimi Tatsuya,
Miura Takashi
Publication year - 1998
Publication title -
cell biochemistry and function
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.933
H-Index - 61
eISSN - 1099-0844
pISSN - 0263-6484
DOI - 10.1002/(sici)1099-0844(199809)16:3<183::aid-cbf784>3.0.co;2-0
Subject(s) - hyperoxia , microbiology and biotechnology , cycloheximide , heme oxygenase , messenger rna , sodium arsenite , chemistry , heme , gene expression , oxygen tension , reactive oxygen species , biology , protein biosynthesis , biochemistry , oxygen , gene , enzyme , arsenic , organic chemistry
The gene expression of heme oxygenase‐1 (HO‐1) was studied in mammalian cell lines exposed to hyperoxia. Northern blot analysis demonstrated that hyperoxic exposure increased the HO‐1 mRNA levels in various types of cells, including human hepatoma (HepG2) cells. This increase was time‐ and dose‐dependent, and reversible. The HO‐1 mRNA levels in HepG2 cells were increased to 2·3‐ and 4·2‐fold of the control by hyperoxic exposure of 6 and 23 h, respectively. Cycloheximide and actinomycin D inhibited the increases in the HO‐1 mRNA level produced by hyperoxia, indicating that response to hyperoxia is dependent on de novo protein synthesis and mRNA transcription. Antioxidants, desferrioxamine (DES) and o ‐phenanthroline (OP) partially inhibited the HO‐1 mRNA elevation by hyperoxia. In addition to hyperoxia, sodium arsenite (NaAsO 2 ), cadmium chloride (CdCl 2 ) and hydrogen peroxide (H 2 O 2 ), which are reactive oxygen intermediates (ROI) generators, increased the HO‐1 mRNA level by 11‐, 22‐ and 2·5‐fold, respectively. OP, an antioxidant and a bivalent metal chelator, blocked the HO‐1 mRNA elevation induced either by hyperoxia or by the three ROI generators. In contrast to OP, N ‐acetylcysteine (NAC), an antioxidant and membrane‐permeable reducing reagent, enhanced the HO‐1 mRNA elevation induced by hyperoxia, although NAC inhibited the mRNA elevation induced by NaAsO 2 , CdCl 2 and H 2 O 2 . These results indicate that oxygen tension regulates HO‐1 gene expression and suggest that hyperoxia‐specific and redox‐sensitive regulators may be involved in hyperoxia‐mediated HO‐1 gene expression. © 1998 John Wiley & Sons, Ltd.