ArticleTranslational stroke research2014
Erythropoietin inhibits HIF-1α expression via upregulation of PHD-2 transcription and translation in an in vitro model of hypoxia-ischemia.
Article in Translational stroke research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 36 citations in OpenAlex.
- <p>Prolyl hydroxylase domain proteins: Localization, regulation, function and their role in erythropoiesis (Review)</p>.Molecular medicine reports · 2026Review
- Deciphering the similarities and disparities of molecular mechanisms behind respiratory epithelium response to HCoV-229E and SARS-CoV-2 and drug repurposing, a systems biology approach.Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences · 2024Article
- Thrombotic Alterations under Perinatal Hypoxic Conditions: HIF and Other Hypoxic Markers.International journal of molecular sciences · 2023Review
- Hypoxia-mediated promotion of glucose metabolism in non-small cell lung cancer correlates with activation of the EZH2/FBXL7/PFKFB4 axis.Cell death & disease · 2023Article
- Astragaloside IV improves angiogenesis under hypoxic conditions by enhancing hypoxia‑inducible factor‑1α SUMOylation.Molecular medicine reports · 2021Article
- The Promoting Effect of Traumatic Brain Injury on the Incidence and Progression of Glioma: A Review of Clinical and Experimental Research.Journal of inflammation research · 2021Review
- Colony-Stimulating Factors on Mobilizing CD34Frontiers in pharmacology · 2021Review
- GW0742 activates miR-17-5p and inhibits TXNIP/NLRP3-mediated inflammation after hypoxic-ischaemic injury in rats and in PC12 cells.Journal of cellular and molecular medicine · 2020Article
- Changes in neurological and pathological outcomes in a modified rat spinal cord injury model with closed canal.Neural regeneration research · 2020Article
- Adenoviral TMBIM6 vector attenuates ER-stress-induced apoptosis in a neonatal hypoxic-ischemic rat model.Disease models & mechanisms · 2019Article
- Viral-mediated gene delivery of TMBIM6 protects the neonatal brain via disruption of NPR-CYP complex coupled with upregulation of Nrf-2 post-HI.Journal of neuroinflammation · 2019Article
- TRAF2 protects against cerebral ischemia-induced brain injury by suppressing necroptosis.Cell death & disease · 2019Article
- Erythropoietin protects neurons from apoptosis via activating PI3K/AKT and inhibiting Erk1/2 signaling pathway.3 Biotech · 2019Article
- Effects of over-expression of HIF-1alpha in bone marrow-derived mesenchymal stem cells on traumatic brain injury.Engineering in life sciences · 2018Article
- Neuroprotective Effects of Bioactive Compounds and MAPK Pathway Modulation in "Ischemia"-Stressed PC12 Pheochromocytoma Cells.Brain sciences · 2018Review
- Recent Advances in Stem Cell-Based Therapeutics for Stroke.Translational stroke research · 2016Article
- Neurodevelopmental implications of the general anesthesia in neonate and infants.Experimental neurology · 2015Review
- What's New in Traumatic Brain Injury: Update on Tracking, Monitoring and Treatment.International journal of molecular sciences · 2015Review
- Effect of intermittent hypoxia on neuro-functional recovery post brain ischemia in mice.Journal of molecular neuroscience : MN · 2015Article
- Erythropoietin in stroke therapy: friend or foe.Current medicinal chemistry · 2015Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Hypoxia inducible factor (HIF)-1α is the central transcriptional factor for the regulation of oxygen-associated genes in response to hypoxia. Erythropoietin (EPO), a hematopoietic growth factor, increases oxygen availability during hypoxia/ischemia and is associated with neuroprotection following hypoxia-ischemia in laboratory models of stroke. However, EPO has failed to translate in a clinical setting. Thus, it is critical to elucidate the key players in EPO-induced neuroprotection. Our preliminary studies have shown that EPO, as a downstream gene of HIF, inhibits HIF-1α in a dose-dependent manner in an in vitro model of hypoxia-ischemia. This study is designed to elucidate the primary mediator of EPO-induced HIF-1α inhibition and subsequent cell survival/neuroprotection. Oxygen and glucose deprivation (OGD) of nerve growth factor-differentiated rat pheochromocytoma (PC-12) cells were used to model hypoxia-ischemia in an in vitro environment. The profile of HIF-1α, HIF-2α and prolyl hydroxylase domain 2 (PHD-2) expression; HIF-1α and prolyl hydroxylase (PHD-2) mRNA levels; matrix metalloproteinase (MMP)-9; and cell death was evaluated in the presence and absence of either EPO or PHD-2 inhibitor during OGD. Our findings showed that EPO treatment resulted in an increase in PHD-2 transcription and translation, inhibition of HIF-1α expression, reactive oxygen species formation, and MMP-9 activity, resulting in increased cell survival after OGD. We also observed that EPO-induced cell survival/neuroprotection was reversed by siRNA silencing of PHD-2. This led to the conclusion that PHD-2 is a key mediator of EPO-induced HIF-1α inhibition and subsequent neuroprotection in an in vitro model of hypoxia-ischemia.
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Registered trials
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