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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Involvement of heme in the transcriptional activation of CYPIIB1/B2 gene by phenobarbitone in rat liver--studies with succinylacetone.

Earlier studies in this laboratory had implicated heme to function as a positive modulator of phenobarbitone-mediated activation of CYPIIB1/B2 gene transcription in rat liver. However, recent reports have indicated that succinylacetone, a specific inhibitor of delta-aminolevulinate dehydrase, does not affect this process. The present studies indicate that succinylacetone does inhibit the phenobarbitone-mediated increase in CYPIIB1/B2 mRNAs and their transcription in rat liver at early time points (45 min to 3 h), but the inhibition is not pronounced at later time points (16 h). Succinylacetone is a weaker inhibitor of heme biosynthesis than CoCl2, 3-amino-1,2,4-triazole, or thioacetamide used earlier in this laboratory. Succinylacetone induces delta-aminolevulinate synthase, whereas the other compounds depress the levels of the enzyme. There is a good correlation between the amount of freshly synthesized nuclear heme pool and the activation of CYPIIB1/B2 transcription by phenobarbitone. A model implicating a nuclear heme pool regulating the transcription of delta-aminolevulinate synthase, CYPIIB1/B2, and heme oxygenase genes is proposed.[1]


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