type	Journal Article
authors	Hofer, T.; Wenger, R. H.; Kramer, M. F.; Ferreira, G. C.; Gassmann, M.
title	Hypoxic upregulation of erythroid 5-aminolevulinate synthase
journal	Blood
Activity	2.3.1.37
ui	Hueas
year	(2002)
volume	29
pages	29
abstract	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% O2) 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.
last changed	2002/11/04 17:51