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Newborns with Favourable Outcomes after Perinatal Asphyxia Have Upregulated Glucose Metabolism-Related Proteins in

Ping K Yip1, Michael Bremang2, Ian Pike2

  • 1Centre for Neuroscience, Surgery and Trauma, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, UK.

Biomolecules
|October 28, 2023
PubMed

Insights

Therapeutic hypothermia (TH) for hypoxic-ischaemic encephalopathy (HIE) shows promise, but its mechanism is unclear. This study found upregulated glucose metabolism proteins in newborns with favorable HIE outcomes after TH, suggesting new therapeutic targets.

Area of Science:

  • Biochemistry and Molecular Biology
  • Neonatal Medicine
  • Proteomics

Background:

  • Hypoxic-ischaemic encephalopathy (HIE) is a significant global cause of newborn morbidity and mortality.
  • Mild therapeutic hypothermia (TH) can improve outcomes in HIE, but its underlying mechanisms require further elucidation.

Purpose of the Study:

  • To investigate the plasma proteome of newborns with HIE undergoing TH to identify mechanisms of neuroprotection.
  • To compare protein profiles between HIE newborns with favorable and unfavorable outcomes following TH.

Main Methods:

  • Plasma samples from newborns with moderate-severe HIE (treated with TH), mild HIE (no TH), and normal controls (cord blood) were analyzed.
  • Isobaric Tandem Mass Tag (TMT®) 10plex™ labeling coupled with tandem mass spectrometry was employed for proteomic analysis.
  • Bioinformatic analysis, including Gene Ontology (GO) annotation and functional clustering, was used to interpret protein data.

Main Results:

  • A total of 405 proteins were identified, with distinct signatures differentiating normal cord blood from HIE groups.
  • Newborns with favorable outcomes (sHIE+) after TH showed significant upregulation of glucose metabolism-related enzymes compared to those with unfavorable outcomes (sHIE-).
  • Specific upregulated enzymes in the sHIE+ group included fructose-bisphosphate aldolase A, glyceraldehyde-3-phosphate dehydrogenase, and pyruvate kinase PKM, among others.

Conclusions:

  • Plasma proteomic analysis reveals an upregulation of glucose metabolism pathways in newborns with favorable outcomes following TH for HIE.
  • These findings suggest that enhanced glucose metabolism may be a key mechanism underlying the neuroprotective effects of TH.
  • The identified proteins may serve as potential biomarkers or therapeutic targets for improving neuroprotection strategies in HIE.

Keywords:
glucose metabolismhypoxic-ischaemic encephalopathyplasmaproteintandem mass spectrometrytherapeutic hypothermia

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