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Oxygen-Dependent Changes in the N-Glycome of Murine Pulmonary Endothelial Cells.

Akos TiboldiJohannes FührerWolfgang SchaubmayrEva Hunyadi-GulyasMarie Louise ZachBeatrix HochreiterAndreas SpittlerRoman UllrichKlaus MarkstallerFriedrich AltmannKlaus Ulrich KleinVerena Tretter
Published in: Antioxidants (Basel, Switzerland) (2021)
Supplemental oxygen is frequently used together with mechanical ventilation to achieve sufficient blood oxygenation. Despite the undoubted benefits, it is vigorously debated whether too much oxygen can also have unpredicted side-effects. Uncertainty is also due to the fact that the molecular mechanisms are still insufficiently understood. The lung endothelium is covered with an exceptionally broad glycocalyx, carrying N- and O-glycans, proteoglycans, glycolipids and glycosaminoglycans. Glycan structures are not genetically determined but depend on the metabolic state and the expression level and activity of biosynthetic and glycan remodeling enzymes, which can be influenced by oxygen and the redox status of the cell. Altered glycan structures can affect cell interactions and signaling. In this study, we investigated the effect of different oxygen conditions on aspects of the glycobiology of the pulmonary endothelium with an emphasis on N-glycans and terminal sialylation using an in vitro cell culture system. We combined a proteomic approach with N-glycan structure analysis by LC-MS, qRT-PCR, sialic acid analysis and lectin binding to show that constant and intermittent hyperoxia induced time dependent changes in global and surface glycosylation. An siRNA approach identified St6gal1 as being primarily responsible for the early transient increase of α2-6 sialylated structures in response to hyperoxia.
Keyphrases
  • cell surface
  • mechanical ventilation
  • high resolution
  • single cell
  • nitric oxide
  • intensive care unit
  • cell therapy
  • poor prognosis
  • stem cells
  • oxidative stress
  • high intensity
  • cancer therapy
  • mass spectrometry
  • bone marrow