Transcriptional control of rat heme oxygenase by heat shock.

A heat shock element is located in the 5'-flanking region of the rat heme oxygenase gene (HO gene). The incubation of rat glioma cells at 42 degrees C or with hemin at 37 degrees C increased the levels of heme oxygenase mRNA within 1 h and produced a maximum at 3 h (at least a 20-fold increase). In both treatments, the heme oxygenase activity started to increase after a lag period of about 1 h and reached a maximum value at 5 h. There was an apparent additive effect of both treatments on the heme oxygenase induction. Studies with actinomycin D and cycloheximide suggested that both heat shock and hemin acted at the transcriptional level to induce heme oxygenase. Therefore, we analyzed the transient expression of chimeric fusion genes harboring the promoter of the rat HO gene ligated to the Escherichia coli gene gpt in rat glioma cells and in K1735 mouse amelanotic melanoma cells. The 5'-flanking region of the rat HO gene bearing the heat shock element conferred the heat inducibility of gpt RNA production in both cell lines; however, hemin treatment did not induce gpt RNA. These results indicate that rat heme oxygenase is a heat shock protein and that hemin induces heme oxygenase through a different mechanism from heat shock.