Linked Life Data

21207956

Source:http://linkedlifedata.com/resource/pubmed/id/21207956

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2011-2-15
pubmed:abstractText
Hypoxia-inducible factor 1 (HIF1) is a heterodimeric basic helix-loop-helix transcription factor that regulates many key genes. ?-Aminolevulinate synthase (ALAS) catalyzes the first and rate-limiting reaction in the heme biosynthetic pathway. In this study, we show that hypoxia-induced expression of erythroid-specific ALAS2 is mediated by HIF1 in erythroid cells. Under hypoxic conditions, significantly increased ALAS2 mRNA and protein levels were detected in K562 cells and erythroid induction cultures of CD34+ hematopoietic stem/progenitor cells. Enforced HIF1? expression increased the level of ALAS2 expression, while HIF1? knockdown by RNA interference decreased the level of ALAS2 expression. In silico analysis revealed three potential hypoxia-response elements (HREs) that are located 611, 621, and 741 bp downstream of the ALAS2 gene. The results from reporter gene and mutation analysis suggested that these elements are necessary for a maximal hypoxic response. Chromatin immunoprecipitation and polymerase chain reaction showed that the HREs could be recognized and bound by HIF1? in vivo. These results demonstrate that the upregulation of ALAS2 during hypoxia is directly mediated by HIF1. We hypothesize that HIF1-mediated ALAS2 upregulation promotes erythropoiesis to satisfy the needs of an organism under hypoxic conditions. This may be accomplished via increased heme levels and an interaction between ALAS2 and erythropoietin.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1520-4995
pubmed:author
pubmed:issnType
Electronic
pubmed:day
22
pubmed:volume
50
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1194-202
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Hypoxic induction of human erythroid-specific ?-aminolevulinate synthase mediated by hypoxia-inducible factor 1.
pubmed:affiliation
National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't