title: Changes in Hypoxia-Inducible Factor-1 (HIF-1) and Regulatory Prolyl Hydroxylase (PHD) Enzymes Following Hypoxic-Ischemic Injury in the Neonatal Rat.
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.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Nursing and Health Services, Monash University, Clayton, VIC, 3800, Australia.
authors.forename: Hannah X
authors.initials: HX
authors.lastname: Chu
authors.affiliation: Department of Pharmacology, School of Medical Sciences, UNSW Australia, Sydney, NSW, 2052, Australia. n.jones@unsw.edu.au.
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Jones
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D064799:Hypoxia-Inducible Factor-Proline Dioxygenases / Q000378:metabolism; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism* / Q000473:pathology; D007527:Isoenzymes / Q000378:metabolism; D064828:Prolyl Hydroxylases / Q000378:metabolism*; D017207:Rats, Sprague-Dawley
chemical_list: C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007527:Isoenzymes; D064828:Prolyl Hydroxylases; C488894:EGLN3 protein, human; D064799:Hypoxia-Inducible Factor-Proline Dioxygenases
keywords: Hypoxia-inducible factor-1; Hypoxia–ischemia; Neonatal brain injury; Prolyl hydroxylase