Linked Life Data

19021769

Source:http://linkedlifedata.com/resource/pubmed/id/19021769

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
23
pubmed:dateCreated
2008-11-21
pubmed:abstractText
Heme is synthesized in all cell types in aerobic organisms. Hydroxymethylbilane synthase (HMBS) and uroporphyrinogen III synthase (UROS) catalyze two consecutive reactions in the heme biosynthetic pathway, generating the first linear and the first cyclic tetrapyrroles, respectively. Each of the HMBS and UROS genes contains the two separate promoters that generate ubiquitous and erythroid-specific mRNAs. Despite the functional significance of HMBS and UROS, regulation of their gene expression remains to be investigated. Here, we showed that hypoxia (1% O(2)) decreased the expression of ubiquitous mRNAs for HMBS and UROS by three- and twofold, respectively, in human hepatic cells (HepG2 and Hep3B), whereas the expression of ubiquitous and erythroid HMBS and UROS mRNAs remained unchanged in erythroid cells (YN-1 and K562). Unexpectedly, hypoxia did not decrease the half-life of HMBS mRNA (8.4 h under normoxia versus 9.1 h under hypoxia) or UROS mRNA (9.0 versus 10.4 h) in hepatic cells. It is therefore unlikely that a change in mRNA stability is responsible for the hypoxia-mediated decrease in the expression levels of these mRNAs. Furthermore, expression levels of HMBS and UROS mRNAs were decreased under normoxia by treatment with deferoxamine or cobalt chloride in hepatic cells, while hypoxia-inducible factor 1alpha was accumulated. Thus, the decrease in the expression of ubiquitous HMBS and UROS mRNAs is associated with accumulation of hypoxia-inducible factor 1alpha protein. In conclusion, the expression of HMBS and UROS mRNAs may be coordinately regulated, which represents a newly identified mechanism that is important for heme homeostasis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1742-4658
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
275
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5947-59
pubmed:meshHeading
pubmed-meshheading:19021769-Blotting, Northern, pubmed-meshheading:19021769-Blotting, Western, pubmed-meshheading:19021769-Cell Hypoxia, pubmed-meshheading:19021769-Cell Line, Tumor, pubmed-meshheading:19021769-Cobalt, pubmed-meshheading:19021769-Deferoxamine, pubmed-meshheading:19021769-Gene Expression Regulation, Enzymologic, pubmed-meshheading:19021769-Heme, pubmed-meshheading:19021769-Humans, pubmed-meshheading:19021769-Hydroxymethylbilane Synthase, pubmed-meshheading:19021769-Isoenzymes, pubmed-meshheading:19021769-Jurkat Cells, pubmed-meshheading:19021769-K562 Cells, pubmed-meshheading:19021769-RNA, Messenger, pubmed-meshheading:19021769-RNA Stability, pubmed-meshheading:19021769-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:19021769-Tetrapyrroles, pubmed-meshheading:19021769-Uroporphyrinogen III Synthetase
pubmed:year
2008
pubmed:articleTitle
Hypoxia decreases the expression of the two enzymes responsible for producing linear and cyclic tetrapyrroles in the heme biosynthetic pathway.
pubmed:affiliation
Department of Molecular Biology and Applied Physiology, Tohoku University School of Medicine, Miyagi, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't