PMID- 26108712 OWN - NLM STAT- MEDLINE DCOM- 20161102 LR - 20181113 IS - 1573-6903 (Electronic) IS - 0364-3190 (Linking) VI - 41 IP - 3 DP - 2016 Mar TI - Changes in Hypoxia-Inducible Factor-1 (HIF-1) and Regulatory Prolyl Hydroxylase (PHD) Enzymes Following Hypoxic-Ischemic Injury in the Neonatal Rat. PG - 515-22 LID - 10.1007/s11064-015-1641-y [doi] AB - 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-1alpha and HIF-1ss subunits and levels of HIF-1alpha protein are regulated by HIF prolyl-hydroxylase enzymes (PHD1, 2, 3). The aim of the current study was to investigate the expression of HIF-1alpha 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 degrees 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-1alpha 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. FAU - Chu, Hannah X AU - Chu HX AD - Department of Pharmacology, Faculty of Medicine, Nursing and Health Services, Monash University, Clayton, VIC, 3800, Australia. FAU - Jones, Nicole M AU - Jones NM AD - Department of Pharmacology, School of Medical Sciences, UNSW Australia, Sydney, NSW, 2052, Australia. n.jones@unsw.edu.au. LA - eng PT - Journal Article DEP - 20150625 PL - United States TA - Neurochem Res JT - Neurochemical research JID - 7613461 RN - 0 (Hif1a protein, rat) RN - 0 (Hypoxia-Inducible Factor 1, alpha Subunit) RN - 0 (Isoenzymes) RN - EC 1.14.11.- (Prolyl Hydroxylases) RN - EC 1.14.11.29 (EGLN3 protein, human) RN - EC 1.14.11.29 (Hypoxia-Inducible Factor-Proline Dioxygenases) SB - IM MH - Animals MH - Animals, Newborn MH - Cerebral Cortex/metabolism/pathology MH - Hypoxia-Inducible Factor 1, alpha Subunit/*metabolism MH - Hypoxia-Inducible Factor-Proline Dioxygenases/metabolism MH - Hypoxia-Ischemia, Brain/*metabolism/pathology MH - Isoenzymes/metabolism MH - Prolyl Hydroxylases/*metabolism MH - Rats, Sprague-Dawley OTO - NOTNLM OT - Hypoxia-inducible factor-1 OT - Hypoxia-ischemia OT - Neonatal brain injury OT - Prolyl hydroxylase EDAT- 2015/06/26 06:00 MHDA- 2016/11/03 06:00 CRDT- 2015/06/26 06:00 PHST- 2015/03/20 00:00 [received] PHST- 2015/06/15 00:00 [accepted] PHST- 2015/06/12 00:00 [revised] PHST- 2015/06/26 06:00 [entrez] PHST- 2015/06/26 06:00 [pubmed] PHST- 2016/11/03 06:00 [medline] AID - 10.1007/s11064-015-1641-y [pii] AID - 10.1007/s11064-015-1641-y [doi] PST - ppublish SO - Neurochem Res. 2016 Mar;41(3):515-22. doi: 10.1007/s11064-015-1641-y. Epub 2015 Jun 25.