ArticleMolecular pharmacology2009
Prolyl hydroxylase inhibitors depend on extracellular glucose and hypoxia-inducible factor (HIF)-2alpha to inhibit cell death caused by nerve growth factor (NGF) deprivation: evidence that HIF-2alpha has a role in NGF-promoted survival of sympathetic neurons.
Article in Molecular pharmacology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 31 citations in OpenAlex.
- Neuroprotective Strategies for Retinal Ganglion Cell Degeneration: Current Status and Challenges Ahead.International journal of molecular sciences · 2020Review
- Hypoxia-Inducible Factor 1α and 2α Have Beneficial Effects in Remote Ischemic Preconditioning Against Stroke by Modulating Inflammatory Responses in Aged Rats.Frontiers in aging neuroscience · 2020Article
- The Role of Endogenous Neuroprotective Mechanisms in the Prevention of Retinal Ganglion Cells Degeneration.Frontiers in neuroscience · 2018Review
- The Inorganic Side of NGF: Copper(II) and Zinc(II) Affect the NGF Mimicking Signaling of the N-Terminus Peptides Encompassing the Recognition Domain of TrkA Receptor.Frontiers in neuroscience · 2016Article
- Ethyl 3,4-dihydroxy benzoate, a unique preconditioning agent for alleviating hypoxia-mediated oxidative damage in L6 myoblasts cells.The journal of physiological sciences : JPS · 2015Article
- Programmed cell death during neuronal development: the sympathetic neuron model.Cell death and differentiation · 2014Review
- Molecular mechanisms of action and therapeutic uses of pharmacological inhibitors of HIF-prolyl 4-hydroxylases for treatment of ischemic diseases.Antioxidants & redox signaling · 2014Review
- The nerve growth factor signaling and its potential as therapeutic target for glaucoma.BioMed research international · 2014Review
- Role of hypoxia and HIF2α in development of the sympathoadrenal cell lineage and chromaffin cell tumors with distinct catecholamine phenotypic features.Advances in pharmacology (San Diego, Calif.) · 2013Review
- Hypoxia inducible factor-1: its potential role in cerebral ischemia.Cellular and molecular neurobiology · 2012Review
- Effect of conjugated linoleic acid on inhibition of prolyl hydroxylase 1 in hearts of mice.Lipids in health and disease · 2012Article
- Article
- Hypoxic regulation of β-1,3-glucuronyltransferase 1 expression in nucleus pulposus cells of the rat intervertebral disc: role of hypoxia-inducible factor proteins.Arthritis and rheumatism · 2011Article
- Cell metabolism: an essential link between cell growth and apoptosis.Biochimica et biophysica acta · 2011Review
- Utilization of an in vivo reporter for high throughput identification of branched small molecule regulators of hypoxic adaptation.Chemistry & biology · 2010Article
- Selective inhibition of hypoxia-inducible factor (HIF) prolyl-hydroxylase 1 mediates neuroprotection against normoxic oxidative death via HIF- and CREB-independent pathways.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2009Article
- Hypoxia inducible factor 1 as a therapeutic target in ischemic stroke.Current medicinal chemistry · 2009Review
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Neurotrophins are critical for the survival of neurons during development and insufficient access to neurotrophins later in life may contribute to the loss of neurons in neurodegenerative disease, spinal cord injury, and stroke. The prolyl hydroxylase inhibitors ethyl 3,4-dihydroxybenzoic acid (DHB) and dimethyloxalylglycine (DMOG) were shown to inhibit cell death in a model of neurotrophin deprivation that involves depriving sympathetic neurons of nerve growth factor (NGF). Here we show that treatment with DMOG or DHB reverses the decline in 2-deoxyglucose uptake caused by NGF withdrawal and suppresses the NGF deprivation-induced accumulation of reactive oxygen species. Neither DMOG nor DHB prevented death when NGF deprivation was carried out under conditions of glucose starvation, and both compounds proved toxic to NGF-maintained neurons deprived of glucose, suggesting that their survival-promoting effects are mediated through the preservation of glucose metabolism. DHB and DMOG are well known activators of hypoxia-inducible factor (HIF), but whether activation of HIF underlies their survival-promoting effects is not known. Using gene disruption and RNA interference, we provide evidence that DMOG and, to a lesser extent, DHB require HIF-2alpha expression to inhibit NGF deprivation-induced death. Furthermore, suppressing basal HIF-2alpha expression, but not HIF-1alpha, in NGF-maintained neurons is sufficient to promote cell death. These results implicate HIF-2alpha in the neuroprotective mechanisms of prolyl hydroxylase inhibitors and in an endogenous cell survival pathway activated by NGF in developing neurons.
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