Regulation of Human Heme Oxygenase-1 Gene Expression Under Thermal Stress

• Published in: Blood 1996-06, Vol.87 (12), p.5074-5084
• Main Authors: Okinaga, Shoji, Takahashi, Kazuhiro, Takeda, Kazuhisa, Yoshizawa, Miki, Fujita, Hiroyoshi, Sasaki, Hidetada, Shibahara, Shigeki
• Format: Article
• Language: English
• Subjects: Base Sequence; Biological and medical sciences; Blast Crisis - pathology; Cadmium - pharmacology; Cell differentiation, maturation, development, hematopoiesis; Cell physiology; Cells, Cultured; DNA-Binding Proteins - metabolism; Enzyme Induction - drug effects; Erythroid Precursor Cells - enzymology; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation, Enzymologic - drug effects; Gene Expression Regulation, Leukemic; Genes, Reporter; Heat Shock Transcription Factors; Heme Oxygenase (Decyclizing) - biosynthesis; Heme Oxygenase (Decyclizing) - genetics; Hot Temperature; HSP70 Heat-Shock Proteins - biosynthesis; HSP70 Heat-Shock Proteins - genetics; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - pathology; Luciferases - biosynthesis; Macrophages, Alveolar - enzymology; Molecular and cellular biology; Molecular Sequence Data; Neoplasm Proteins - biosynthesis; Neoplasm Proteins - genetics; Promoter Regions, Genetic; Recombinant Fusion Proteins - biosynthesis; Sequence Deletion; Transcription Factors; Tumor Cells, Cultured
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V87.12.5074.bloodjournal87125074

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°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 mRIMA 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.