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PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2000-10-3
pubmed:abstractText
The mechanisms by which excitable cells adapt and respond to changes in O2 levels remain largely unknown. We have investigated the effect of hypoxia on the cyclic AMP response element binding protein (CREB) transcription factor. PC12 cells were exposed to moderate levels of hypoxia (5% O2) for various times between 20 min and 6 hr. We found that hypoxia rapidly and persistently induced ser133 phosphorylation of CREB. This effect was more robust than that produced by exposing PC12 cells to either forskolin, KCl, or NGF. This effect was not due to activation of any of the previously known CREB kinases, including PKA, CaMK, PKC, p70s6k, or MAPKAP kinase-2. Thus, hypoxia may induce activation of a novel CREB kinase. To test whether phosphorylation of CREB was associated with an activation of CRE-dependent gene expression, cells were transfected with wild type and mutated regions of the 5'-flanking region of the tyrosine hydroxylase (TH) gene fused to a CAT reporter gene. Mutation of the CRE element in a TH reporter gene reduced, but did not abolish, the effects of hypoxia on TH gene expression. However, hypoxia did not induce transactivation of a GAL4-luciferase reporter by a GAL4-CREB fusion protein. Thus, the mechanism by which hypoxia regulates CREB is distinct, and more complex, than that induced by forskolin, depolarization, or nerve growth factor.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Chloramphenicol O-Acetyltransferase, http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP Response..., http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Fungal Proteins, http://linkedlifedata.com/resource/pubmed/chemical/GAL4 protein, S cerevisiae, http://linkedlifedata.com/resource/pubmed/chemical/Luciferases, http://linkedlifedata.com/resource/pubmed/chemical/Ribosomal Protein S6 Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Saccharomyces cerevisiae Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Serine, http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors, http://linkedlifedata.com/resource/pubmed/chemical/Tyrosine 3-Monooxygenase
pubmed:status
MEDLINE
pubmed:issn
0065-2598
pubmed:author
pubmed:issnType
Print
pubmed:volume
475
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
143-52
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:10849656-Animals, pubmed-meshheading:10849656-Artificial Gene Fusion, pubmed-meshheading:10849656-Cell Hypoxia, pubmed-meshheading:10849656-Chloramphenicol O-Acetyltransferase, pubmed-meshheading:10849656-Cyclic AMP Response Element-Binding Protein, pubmed-meshheading:10849656-DNA-Binding Proteins, pubmed-meshheading:10849656-Enzyme Activation, pubmed-meshheading:10849656-Fungal Proteins, pubmed-meshheading:10849656-Gene Expression, pubmed-meshheading:10849656-Genes, Reporter, pubmed-meshheading:10849656-Luciferases, pubmed-meshheading:10849656-Models, Biological, pubmed-meshheading:10849656-PC12 Cells, pubmed-meshheading:10849656-Phosphorylation, pubmed-meshheading:10849656-Rats, pubmed-meshheading:10849656-Ribosomal Protein S6 Kinases, pubmed-meshheading:10849656-Saccharomyces cerevisiae Proteins, pubmed-meshheading:10849656-Serine, pubmed-meshheading:10849656-Signal Transduction, pubmed-meshheading:10849656-Transcription Factors, pubmed-meshheading:10849656-Transfection, pubmed-meshheading:10849656-Tyrosine 3-Monooxygenase
pubmed:year
2000
pubmed:articleTitle
Regulation of CREB by moderate hypoxia in PC12 cells.
pubmed:affiliation
Department of Molecular and Cellular Physiology, College of Medicine, University of Cincinnati, OH 45267-0576, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't