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

Ping K Yip; Michael Bremang; Ian Pike; Vennila Ponnusamy; Adina T Michael-Titus; Divyen K Shah

doi:10.3390/biom13101471

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

Biomolecules. 2023 Sep 30;13(10):1471. doi: 10.3390/biom13101471.

Authors

Ping K Yip¹, Michael Bremang², Ian Pike², Vennila Ponnusamy^{1

3}, Adina T Michael-Titus¹, Divyen K Shah^{1

4}

Affiliations

¹ Centre 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.
² Proteome Sciences PLC, Coveham House, Surrey KT11 3EP, UK.
³ St. Peter's Hospital (Ashford and St. Peter's Hospitals NHS Foundation Trust), Chertsey KT16 0PZ, UK.
⁴ Neonatal Unit, Royal London Hospital, Barts Health NHS Trust, London E1 1FR, UK.

Abstract

Hypoxic-ischaemic encephalopathy (HIE) is an important cause of morbidity and mortality globally. Although mild therapeutic hypothermia (TH) may improve outcomes in selected babies, the mechanism of action is not fully understood. A proteomics discovery study was carried out to analyse proteins in the plasma of newborns with HIE. Proteomic analysis of plasma from 22 newborns with moderate-severe HIE that had initially undergone TH, and relative controls including 10 newborns with mild HIE who did not warrant TH and also cord blood from 10 normal births (non-HIE) were carried out using the isobaric Tandem Mass Tag (TMT^®) 10plex^TM labelling with tandem mass spectrometry. A total of 7818 unique peptides were identified in all TMT10plex^TM samples, translating to 3457 peptides representing 405 proteins, after applying stringent filter criteria. Apart from the unique protein signature from normal cord blood, unsupervised analysis revealed several significantly regulated proteins in the TH-treated moderate-severe HIE group. GO annotation and functional clustering revealed various proteins associated with glucose metabolism: the enzymes fructose-bisphosphate aldolase A, glyceraldehyde-3-phosphate dehydrogenase, phosphoglycerate mutase 1, phosphoglycerate kinase 1, and pyruvate kinase PKM were upregulated in newborns with favourable (sHIE+) outcomes compared to newborns with unfavourable (sHIE-) outcomes. Those with favourable outcomes had normal MR imaging or mild abnormalities not predictive of adverse outcomes. However, in comparison to mild HIE and the sHIE- groups, the sHIE+ group had the additional glucose metabolism-related enzymes upregulated, including triosephosphate isomerase, α-enolase, 6-phosphogluconate dehydrogenase, transaldolase, and mitochondrial glutathione reductase. In conclusion, our plasma proteomic study demonstrates that TH-treated newborns with favourable outcomes have an upregulation in glucose metabolism. These findings may open new avenues for more effective neuroprotective therapy.

Keywords: glucose metabolism; hypoxic-ischaemic encephalopathy; plasma; protein; tandem mass spectrometry; therapeutic hypothermia.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Asphyxia*
Carbohydrate Metabolism
Humans
Infant
Infant, Newborn
Peptides
Proteomics*
Tandem Mass Spectrometry

Substances

Peptides

Grants and funding

This study was funded by the National Institute for Health Research (NIHR) Brain Injury Healthcare Technology Co-operative and Barts Charity.