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Title of Journal: Mol Cell Biochem

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Abbravation: Molecular and Cellular Biochemistry

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Springer US

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DOI

10.1007/bf02448279

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ISSN

1573-4919

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Differential regulation of human ALAS1 mRNA and pr

Authors: Jianyu Zheng Ying Shan Richard W Lambrecht Susan E Donohue Herbert L Bonkovsky
Publish Date: 2008/08/22
Volume: 319, Issue: 1-2, Pages: 153-161
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Abstract

5Aminolevulinic acid synthase 1 ALAS1 is the first and ratecontrolling enzyme of heme biosynthesis This study was to determine the effects of heme and selected nonheme metalloporphyrins on human ALAS1 gene expression in hepatocytes We found that upon heme and cobalt protoporphyrin CoPP treatments ALAS1 mRNA levels were downregulated significantly by ca 50 or more Measurement of mRNA in the presence of actinomycin D showed that these downregulations were due to the decreases in mRNA halflives Furthermore the levels of mitochondrial mature ALAS1 protein were downregulated by 60–70 but those of the cytosolic precursor protein were upregulated by 2–5fold Measurement of protein in the presence of cycloheximide CHX suggests that elevation of the precursor form is due to the increase in protein halflives These results provide novel insights into the mechanisms of heme repressional effects on ALAS1 and provide a rationale for further investigation of CoPP as a therapeutic agent for acute porphyric syndromes

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