RGD Reference Report - Hypoxia inducible factor (HIF)-2 alpha is required for the development of the catecholaminergic phenotype of sympathoadrenal cells. - Rat Genome Database

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Hypoxia inducible factor (HIF)-2 alpha is required for the development of the catecholaminergic phenotype of sympathoadrenal cells.

Authors: Brown, ST  Kelly, KF  Daniel, JM  Nurse, CA 
Citation: Brown ST, etal., J Neurochem. 2009 Jul;110(2):622-30. Epub 2009 May 8.
RGD ID: 5128877
Pubmed: PMID:19457096   (View Abstract at PubMed)
DOI: DOI:10.1111/j.1471-4159.2009.06153.x   (Journal Full-text)

The basic helix-loop-helix transcription factor, hypoxia inducible factor (HIF)-2alpha has been implicated in the development of the catecholaminergic phenotype in cells of the sympathoadrenal (SA) lineage; however, the underlying mechanisms and HIF-2alpha targets remain unclear. Using an immortalized rat adrenomedullary chromaffin cell line (MAH cells) derived from a fetal SA progenitor, we examined the role of HIF-2alpha in catecholamine biosynthesis. Chronic hypoxia (2% O(2), 24 h) induced HIF-2alpha in MAH cells but expression of the rate-limiting enzyme, tyrosine hydroxylase (TH) and catecholamine levels were unaltered. Interestingly, HIF-2alpha depleted MAH cells showed dramatically lower (5-12 times) levels of dopamine and noradrenaline compared with wild-type and scrambled controls, even in normoxia (21% O(2)). This was correlated with a marked reduction in the expression of DOPA decarboxylase (DDC) and dopamine beta hydroxylase (DbetaH) but not TH. Chromatin immunoprecipitation assays revealed that HIF-2alpha was bound to the DDC gene promoter which contains two putative hypoxia response elements. These data suggest that a basal level of HIF-2alpha function is required for the normal developmental expression of DDC and DbetaH in SA progenitor cells, and that loss of this function leads to impaired catecholamine biosynthesis.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Epas1Ratnorepinephrine biosynthetic process  IMP  RGD 
Epas1Ratpositive regulation of dopamine biosynthetic process  IMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Epas1  (endothelial PAS domain protein 1)

Objects referenced in this article
Gene Dbh dopamine beta-hydroxylase Rattus norvegicus
Gene Ddc dopa decarboxylase Rattus norvegicus

Additional Information