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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
- Source :
- Neurochemical Research. 41:515-522
- Publication Year :
- 2015
- Publisher :
- Springer Science and Business Media LLC, 2015.
-
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.
- Subjects :
- 0301 basic medicine
Hypoxia-Inducible Factor 1
medicine.medical_specialty
Pathology
Biology
Biochemistry
Prolyl Hydroxylases
Hypoxia-Inducible Factor-Proline Dioxygenases
Rats, Sprague-Dawley
03 medical and health sciences
Cellular and Molecular Neuroscience
0302 clinical medicine
Internal medicine
medicine
Animals
Transcription factor
Cerebral Cortex
chemistry.chemical_classification
Hypoxic ischemic
Neonatal rat
Right carotid artery occlusion
General Medicine
Hypoxia (medical)
Hypoxia-Inducible Factor 1, alpha Subunit
Isoenzymes
Blot
030104 developmental biology
Enzyme
Endocrinology
Animals, Newborn
chemistry
Hypoxia-Ischemia, Brain
medicine.symptom
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 15736903 and 03643190
- Volume :
- 41
- Database :
- OpenAIRE
- Journal :
- Neurochemical Research
- Accession number :
- edsair.doi.dedup.....e813693e53ba2d8ff8d26100a6426aa5