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Co‐regulation of heme oxygenase and erythropoietin genes
Author(s) -
Abraham N. G.,
Levere R. D.,
Lin J. H.C.,
Beru N.,
Hermine O.,
Goldwasser E.
Publication year - 1991
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.240470106
Subject(s) - heme oxygenase , oxygenase , heme , transcription (linguistics) , messenger rna , chemistry , kidney , microbiology and biotechnology , northern blot , erythropoietin , gene expression , gene , biochemistry , biology , enzyme , endocrinology , linguistics , philosophy
The mechanism responsible for the accumulation of heme oxygenase and erythropoietin (epo) transcripts due to cobalt chloride (CoCl 2 ) 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 CoCl 2 . 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 CoCl 2 . 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 CoCl 2 administration. Transcription of the heme oxygenase gene is greatly increased in rat kidney within 1 hr of administration of CoCl 2 as evidenced from the levels of 32 P‐UTP incorporation into the specific transcript. Time course studies showed that stimulation of transcription was increased about fortyfold 3 hr after CoCl 2 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 CoCl 2 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 CoCl 2 administration. The fact that CoCl 2 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.