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Changes in Hypoxia-Inducible Factor-1 (HIF-1) and Regulatory Prolyl Hydroxylase (PHD) Enzymes Following Hypoxic–Ischemic Injury in the Neonatal Rat

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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.

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Authors and Affiliations

  1. Department of Pharmacology, Faculty of Medicine, Nursing and Health Services, Monash University, Clayton, VIC, 3800, Australia

    Hannah X. Chu

  2. Department of Pharmacology, School of Medical Sciences, UNSW Australia, Sydney, NSW, 2052, Australia

    Nicole M. Jones

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  1. Hannah X. Chu
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  2. Nicole M. Jones
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Correspondence to Nicole M. Jones.

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Special Issue: In honor of Dr. Philip Beart.

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Chu, H.X., Jones, N.M. Changes in Hypoxia-Inducible Factor-1 (HIF-1) and Regulatory Prolyl Hydroxylase (PHD) Enzymes Following Hypoxic–Ischemic Injury in the Neonatal Rat. Neurochem Res 41, 515–522 (2016). https://doi.org/10.1007/s11064-015-1641-y

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  • DOI: https://doi.org/10.1007/s11064-015-1641-y

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