Journal of cellular biochemistryJan 13, 2006

Cells from the spinal disc produce HIF-1 alpha even in normal oxygen, showing a metabolic adjustment to their disc environment

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Updated Mar 29, 2026

Abstract

Nucleus pulposus cells in a low oxygen environment show minimal induction of HIF-1alpha protein levels.

HIF-1alpha is a transcription factor that regulates energy metabolism in cells.
Nucleus pulposus cells from rat, human, and sheep express HIF-1alpha consistently under normal oxygen conditions.
Under low oxygen conditions, nucleus pulposus cells demonstrate only a minimal increase in HIF-1alpha protein levels compared to other cell types.
HIF-1alpha protein binds to its DNA target in normoxic conditions, indicating functional activity.
Increased transcriptional activity of HIF-1alpha is observed under hypoxic conditions, though the response is limited compared to other cell lines.
HIF-1alpha may serve as a phenotypic marker for nucleus pulposus cells.

Simplified

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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Cells from the spinal disc produce HIF-1 alpha even in normal oxygen, showing a metabolic adjustment to their disc environment

Abstract

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