Changes in hypoxia-inducible factor-1 (HIF-1) and regulatory prolyl hydroxylase (PHD) enzymes following hypoxic-ischemic injury in the neonatal rat

Hannah X. Chu, Nicole M. Jones

Research output: Contribution to journalArticleResearchpeer-review

8 Citations (Scopus)

Abstract

Hypoxia leads to activation of many cellular adaptive processes which are regulated by the transcription factor hypoxia-inducible factor-1 (HIF-1). HIF-1 consists of HIF-1α and HIF-1ß subunits and levels of HIF-1α protein are regulated by HIF prolyl-hydroxylase enzymes (PHD1, 2, 3). The aim of the current study was to investigate the expression of HIF-1α and PHDs at various time points after hypoxia–ischemia (HI), using a neonatal rat model of HI brain injury. Sprague–Dawley rat pups (postnatal day 7) were anaesthetized and underwent right carotid artery occlusion and were then exposed to 6 % oxygen for 2.5 h at 37 °C. HI injured animals demonstrated a significant reduction in the size of the ipsilateral hemisphere, compared to sham controls. Protein analysis using western blotting and enzyme-linked immunosorbent assay showed that 24 h after HI, there was a significant increase in PHD3 protein and an increase of HIF-1α compared to controls. At the 72 h time point, there was a reduction in PHD3 protein, which appeared to relate to cellular loss. There were no changes in PHD1 or PHD2 protein levels after HI when compared to age-matched controls. Further studies are necessary to establish roles for the HIF-1 regulatory enzyme PHD3 in brain injury processes.
Original languageEnglish
Pages (from-to)515-522
Number of pages8
JournalNeurochemical Research
Volume41
Issue number3
DOIs
Publication statusPublished - Mar 2016

Keywords

  • hypoxia-ischemia
  • neonatal brain injury
  • hypoxia-inducible factor-1
  • prolyl hydroxylase

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