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Endothelial cell hypoxic stress proteins

K K Graven1, H W Farber

  • 1The Pulmonary Center, Boston University School of Medicine, Massachusetts, USA.

The Journal of Laboratory and Clinical Medicine
|December 16, 1998
PubMed
Summary

Endothelial cells (ECs) adapt to low oxygen (hypoxia) by producing unique stress proteins, including glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and non-neuronal enolase (NNE). These hypoxia-associated proteins (HAPs) may have roles beyond glycolysis.

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Area of Science:

  • Cellular Biology
  • Physiology
  • Biochemistry

Background:

  • Vascular endothelium regulates vascular tone, inflammation, permeability, angiogenesis, and hemostasis.
  • Endothelial cell (EC) function is sensitive to oxygen tension and local cellular environment.
  • ECs exhibit remarkable hypoxia tolerance, but the underlying mechanisms are poorly understood.

Purpose of the Study:

  • To investigate the mechanisms by which ECs respond and adapt to hypoxia.
  • To identify and characterize hypoxia-associated proteins (HAPs) in ECs.
  • To explore potential non-glycolytic functions of identified HAPs.

Main Methods:

  • Cultured ECs were exposed to hypoxic conditions.
  • Hypoxia-associated proteins (HAPs) were identified and quantified.

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  • Gene expression regulation (transcription vs. mRNA accumulation) was analyzed for GAPDH and NNE.
  • Subcellular fractionation was used to determine the localization of HAPs.
  • Main Results:

    • Hypoxia induces a distinct set of HAPs in ECs, including glycolytic enzymes glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and non-neuronal enolase (NNE).
    • GAPDH expression is transcriptionally regulated during hypoxia, while NNE mRNA accumulation mechanisms are unclear.
    • HAPs are upregulated by transitional metals and deferoxamine, but not inhibited by carbon monoxide.
    • Subcellular fractionation revealed GAPDH and NNE in the cytoplasm, with GAPDH also detected in the nucleus, suggesting non-glycolytic roles.

    Conclusions:

    • ECs upregulate specific HAPs, such as GAPDH and NNE, as a response to hypoxia.
    • The nuclear localization of GAPDH suggests functions beyond its role in glycolysis.
    • The upregulation of HAPs may contribute to the hypoxia tolerance of ECs, distinguishing them from more sensitive cell types.