Source:http://linkedlifedata.com/resource/pubmed/id/16408279
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rdf:type | |
lifeskim:mentions |
umls-concept:C0007634,
umls-concept:C0010453,
umls-concept:C0017262,
umls-concept:C0021815,
umls-concept:C0215848,
umls-concept:C0311400,
umls-concept:C0348080,
umls-concept:C0392673,
umls-concept:C1171362,
umls-concept:C1185714,
umls-concept:C1515670,
umls-concept:C1822686,
umls-concept:C2003941,
umls-concept:C2348110,
umls-concept:C2348977
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pubmed:issue |
1
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pubmed:dateCreated |
2006-4-12
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pubmed:abstractText |
Nucleus pulposus (NP) cells of the intervertebral disc reside in an environment that has a limited vascular supply and generate energy through anaerobic glycolysis. The goal of the present study was to examine the expression and regulation of HIF-1alpha, a transcription factor that regulates oxidative metabolism in nucleus pulposus cells. Nucleus pulposus cells were isolated from rat, human, and sheep disc and maintained at either 21% or 2% oxygen for various time periods. Cells were also treated with desferrioxamine (Dfx), a compound that mimics the effects of hypoxia (Hx). Expression and function of HIF-1alpha were assessed by immunofluorescence microscopy, Western blot analysis, gel shift assays, and luciferase reporter assays. In normoxia (Nx), rat, sheep, and human nucleus pulposus cells consistently expressed the HIF-1alpha subunit. Unlike other skeletal cells, when maintained under low oxygen tension, the nucleus pulposus cells exhibited a minimal induction in HIF-1alpha protein levels. Electromobility shift assays confirmed the functional binding of normoxic HIF-1alpha protein to its putative DNA binding motif. A dual luciferase reporter assay showed increased HIF-1alpha transcriptional activity under hypoxia compared to normoxic level, although this induction was small when compared to HeLa and other cell types. These results indicate that normoxic stabilization of HIF-1alpha is a metabolic adaptation of nucleus pulposus cells to a unique oxygen-limited microenvironment. The study confirmed that HIF-1alpha can be used as a phenotypic marker of nucleus pulposus cells.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0730-2312
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
98
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
152-9
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:16408279-Adaptation, Physiological,
pubmed-meshheading:16408279-Animals,
pubmed-meshheading:16408279-Anoxia,
pubmed-meshheading:16408279-Cell Differentiation,
pubmed-meshheading:16408279-Cells, Cultured,
pubmed-meshheading:16408279-HeLa Cells,
pubmed-meshheading:16408279-Humans,
pubmed-meshheading:16408279-Hypoxia-Inducible Factor 1, alpha Subunit,
pubmed-meshheading:16408279-Intervertebral Disc,
pubmed-meshheading:16408279-Male,
pubmed-meshheading:16408279-Oxygen,
pubmed-meshheading:16408279-Phenotype,
pubmed-meshheading:16408279-Rats,
pubmed-meshheading:16408279-Rats, Wistar
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pubmed:year |
2006
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pubmed:articleTitle |
Nucleus pulposus cells express HIF-1 alpha under normoxic culture conditions: a metabolic adaptation to the intervertebral disc microenvironment.
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pubmed:affiliation |
Department of Orthopaedic Surgery and Graduate Program in Tissue Engineering and Regenerative Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania, 19107.
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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