Co-regulation of heme oxygenase and erythropoietin genes

✍ Scribed by N. G. Abraham; R. D. Levere; J. H.-C. Lin; N. Beru; O. Hermine; E. Goldwasser

• Publisher: John Wiley and Sons
• Year: 1991
• Tongue: English
• Weight: 611 KB
• Volume: 47
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/jcb.240470106

✦ Synopsis

The mechanism responsible for the accumulation of heme oxygenase and erythropoietin (epo) transcripts due to cobalt chloride (CoCI,) administration was investigated in rat kidney using a rat heme oxygenase and mouse epo probes. We found an increase of heme oxygenase transcripts in kidney in response to CoCI,. Quantitative evaluation of the heme oxygenase mRNA changes, by scanning densitometry, indicated that the levels of mRNA encoding heme oxygenase were increased by about fiftyfold in rat kidney after administration of CoCI,. That the increase in heme oxygenase mRNA levels resulted from enhanced transcription of the heme oxygenase gene was confirmed by nuclear runoff using isolated rat kidney nuclei after CoCI, administration. Transcription of the heme oxygenase gene i s greatly increased in rat kidney within 1 hr of administration of CoCI, as evidenced from the levels of 32P-UTP incorporation into the specific transcript. Time course studies showed that stimulation of transcription was increased about fortyfold 3 hr after CoCI, administration. This stimulation is the most rapid transcriptional response to heavy metals yet described. In addition, Northern blot analysis demonstrated that epo mRNA was first detected 4 hr following CoCI, administration and reached a maximum at 5 hr. On the other hand, PCR analysis indicated that epo mRNA was increased as early as 1 hr following CoCI, administration. The fact that CoCI, caused increased transcription of both the epo and heme oxygenase genes suggests that a common mechanism may be involved in the regulation of these two genes by the heavy metal ion.