Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-48
Hofer, T; Wenger, R H; Kramer, M F; Ferreira, G C; Gassmann, M (2003). Hypoxic up-regulation of erythroid 5-aminolevulinate synthase. Blood, 101(1):348-350.
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The erythroid-specific isoform of 5-aminolevulinate synthase (ALAS2) catalyzes the rate-limiting step in heme biosynthesis. The hypoxia-inducible factor-1 (HIF-1) transcriptionally up-regulates erythropoietin, transferrin, and transferrin receptor, leading to increased erythropoiesis and hematopoietic iron supply. To test the hypothesis that ALAS2 expression might be regulated by a similar mechanism, we exposed murine erythroleukemia cells to hypoxia (1% O(2)) and found an up to 3-fold up-regulation of ALAS2 mRNA levels and an increase in cellular heme content. A fragment of the ALAS2 promoter ranging from -716 to +1 conveyed hypoxia responsiveness to a heterologous luciferase reporter gene construct in transiently transfected HeLa cells. In contrast, iron depletion, known to induce HIF-1 activity but inhibit ALAS2 translation, did not increase ALAS2 promoter activity. Mutation of a previously predicted HIF-1-binding site (-323/-318) within this promoter fragment and DNA-binding assays revealed that hypoxic up-regulation is independent of this putative HIF-1 DNA-binding site.
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|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||05 Vetsuisse Faculty > Institute of Veterinary Physiology|
|Dewey Decimal Classification:||570 Life sciences; biology|
|Deposited On:||11 Feb 2008 12:12|
|Last Modified:||05 Apr 2016 12:12|
|Publisher:||American Society of Hematology|
|Additional Information:||This research was originally published in Blood, 2003; 101(1):348-350. Copyright by the American Society of Hematology|
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