| Nucleus pulposus cells express HIF-1 alpha under normoxic culture conditions: a metabolic adaptation to the intervertebral disc microenvironment. | |
| | |
MedLine Citation:
|
PMID: 16408279 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
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. |
| | |
Authors:
|
Makarand V Risbud; Asha Guttapalli; David G Stokes; David Hawkins; Keith G Danielson; Thomas P Schaer; Todd J Albert; Irving M Shapiro |
Related Documents
:
|
7647919 - Detection of hydroxyl radical in intact cells of chlorella vulgaris. 19540039 - Chemoradiation interactions under reduced oxygen conditions: cellular characteristics o... 3164049 - Mitogenic response of cells in culture to demineralized bone matrix. 14745499 - Hopes, disillusions and more hopes from vitamin c. 17174349 - Oxygen delivery through capillaries. 19846259 - Do monoamine-synthesizing cells constitute a complex network of oxygen sensors? 22262829 - Cocaine sensitization inhibits the hyperpolarization-activated cation current ih and re... 122509 - Phosphoenolpyruvate and 2-phosphoglycerate: endogenous energy source(s) for sugar accum... 1879939 - Isolation of an intracellular bacterium from hamsters (mesocricetus auratus) with proli... |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural |
Journal Detail:
|
Title: Journal of cellular biochemistry Volume: 98 ISSN: 0730-2312 ISO Abbreviation: J. Cell. Biochem. Publication Date: 2006 May |
Date Detail:
|
Created Date: 2006-04-12 Completed Date: 2009-05-29 Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 8205768 Medline TA: J Cell Biochem Country: United States |
Other Details:
|
Languages: eng Pagination: 152-9 Citation Subset: IM |
Affiliation:
|
Department of Orthopaedic Surgery and Graduate Program in Tissue Engineering and Regenerative Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania, 19107. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Adaptation, Physiological* Animals Anoxia / metabolism Cell Differentiation / genetics Cells, Cultured Hela Cells Humans Hypoxia-Inducible Factor 1, alpha Subunit / biosynthesis, genetics*, metabolism* Intervertebral Disk / chemistry*, cytology*, metabolism Male Oxygen / metabolism* Phenotype Rats Rats, Wistar |
| Grant Support | |
ID/Acronym/Agency:
|
R01-AR050087/AR/NIAMS NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Hypoxia-Inducible Factor 1, alpha Subunit; 7782-44-7/Oxygen |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Force meets chemistry: analysis of mechanochemical conversion in focal adhesions using fluorescence ...
Next Document: The significance of telomeric aggregates in the interphase nuclei of tumor cells.