Regulation of human heme oxygenase-1 gene expression under thermal stress.
Heme oxygenase-1 is an essential enzyme in heme catabolism, and its human gene promoter contains a putative heat shock element (HHO-HSE). This study was designed to analyze the regulation of human heme oxygenase-1 gene expression under thermal stress. The amounts of heme oxygenase-1 protein were not increased by heat shock (incubation at 42 degrees C) in human alveolar macrophages and in a human erythroblastic cell line, YN-1-0-A, whereas heat shock protein 70 (HSP70) was noticeably induced. However, heat shock factor does bind in vitro to HHO-HSE and the synthetic HHO-HSE by itself is sufficient to confer the increase in the transient expression of a reporter gene upon heat shock. The deletion of the sequence, located downstream from HHO-HSE, resulted in the activation of a reporter gene by heat shock. These results suggest that HHO-HSE is potentially functional but is repressed in vivo. Interestingly, heat shock abolished the remarkable increase in the levels of heme oxygenase-1 mRNA in YN-1-0-A cells treated with hemin or cadmium, in which HSP70 mRNA was noticeably induced. Furthermore, transient expression assays showed that heat shock inhibits the cadmium-mediated activation of the heme oxygenase-1 promoter, whereas the HSP70 gene promoter was activated upon heat shock. Such regulation of heme oxygenase-1 under thermal stress may be of physiologic significance in erythroid cells.
Okinaga
S
S
Department of Applied Physiology and Molecular Biology, Tohoku University School of Medicine, Japan.
Takahashi
K
K
Takeda
K
K
Yoshizawa
M
M
Fujita
H
H
Sasaki
H
H
Shibahara
S
S
D001483:Base Sequence; D001752:Blast Crisis / Q000473:pathology; D002104:Cadmium / Q000494:pharmacology; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism; D004790:Enzyme Induction / Q000187:drug effects; D015672:Erythroid Precursor Cells / Q000201:enzymology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D015973:Gene Expression Regulation, Leukemic; D017930:Genes, Reporter; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis / Q000235:genetics; D000076249:Heat Shock Transcription Factors; D006419:Heme Oxygenase (Decyclizing) / Q000096:biosynthesis* / Q000235:genetics; D006358:Hot Temperature; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000473:pathology; D008156:Luciferases / Q000096:biosynthesis; D016676:Macrophages, Alveolar / Q000201:enzymology*; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D011401:Promoter Regions, Genetic; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D017384:Sequence Deletion; D014157:Transcription Factors; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D018840:HSP70 Heat-Shock Proteins; D000076249:Heat Shock Transcription Factors; D009363:Neoplasm Proteins; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D002104:Cadmium; D008156:Luciferases; D006419:Heme Oxygenase (Decyclizing)