PMID- 12393745
OWN - NLM
STAT- MEDLINE
DCOM- 20030318
LR  - 20210206
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 101
IP  - 1
DP  - 2003 Jan 1
TI  - Hypoxic up-regulation of erythroid 5-aminolevulinate synthase.
PG  - 348-50
AB  - 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.
FAU - Hofer, Thomas
AU  - Hofer T
AD  - Institute of Veterinary Physiology, University of Zurich, Switzerland.
FAU - Wenger, Roland H
AU  - Wenger RH
FAU - Kramer, Marianne F
AU  - Kramer MF
FAU - Ferreira, Gloria C
AU  - Ferreira GC
FAU - Gassmann, Max
AU  - Gassmann M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20020829
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hif1a protein, mouse)
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Nuclear Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Transcription Factors)
RN  - 42VZT0U6YR (Heme)
RN  - E1UOL152H7 (Iron)
RN  - EC 2.3.1.37 (5-Aminolevulinate Synthetase)
SB  - IM
MH  - 5-Aminolevulinate Synthetase/*genetics
MH  - Animals
MH  - DNA-Binding Proteins
MH  - Erythrocytes/*enzymology
MH  - HeLa Cells
MH  - Heme/metabolism
MH  - Humans
MH  - Hypoxia/*enzymology
MH  - Hypoxia-Inducible Factor 1
MH  - Hypoxia-Inducible Factor 1, alpha Subunit
MH  - Iron/pharmacology
MH  - Mice
MH  - Nuclear Proteins
MH  - Promoter Regions, Genetic
MH  - RNA, Messenger/biosynthesis
MH  - *Transcription Factors
MH  - *Up-Regulation
EDAT- 2002/10/24 04:00
MHDA- 2003/03/19 04:00
CRDT- 2002/10/24 04:00
PHST- 2002/10/24 04:00 [pubmed]
PHST- 2003/03/19 04:00 [medline]
PHST- 2002/10/24 04:00 [entrez]
AID - S0006-4971(20)53606-9 [pii]
AID - 10.1182/blood-2002-03-0773 [doi]
PST - ppublish
SO  - Blood. 2003 Jan 1;101(1):348-50. doi: 10.1182/blood-2002-03-0773. Epub 2002 Aug 
      29.