ArticleJournal of molecular neuroscience : MN2010
Oxygen tension modulates neurite outgrowth in PC12 cells through a mechanism involving HIF and VEGF.
Article in Journal of molecular neuroscience : MN, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 29 citations in OpenAlex.
- Dimethyloxalylglycine (DMOG), a Hypoxia Mimetic Agent, Does Not Replicate a Rat Pheochromocytoma (PC12) Cell Biological Response to Reduced Oxygen Culture.Biomolecules · 2022Article
- Hypoxic stress enhances extension and branching of dorsal root ganglion neuronal outgrowth.JOR spine · 2020Article
- Oxygen-Glucose Deprivation/Reoxygenation-Induced Barrier Disruption at the Human Blood-Brain Barrier is Partially Mediated Through the HIF-1 Pathway.Neuromolecular medicine · 2019Article
- Bioprocessing strategies to enhance the challenging isolation of neuro-regenerative cells from olfactory mucosa.Scientific reports · 2018Article
- VEGF expression correlates with neuronal differentiation and predicts a favorable prognosis in patients with neuroblastoma.Scientific reports · 2017Article
- Hypoxia-inducible factor-1a contributes to dendritic overgrowth in tuberous sclerosis.Neuroscience letters · 2016Article
- Sulfated Polysaccharide Isolated from the Sea Cucumber Stichopus japonicus Against PC12 Hypoxia/Reoxygenation Injury by Inhibition of the MAPK Signaling Pathway.Cellular and molecular neurobiology · 2015Article
- Calreticulin Regulates VEGF-A in Neuroblastoma Cells.Molecular neurobiology · 2015Article
- Applications of azo-based probes for imaging retinal hypoxia.ACS medicinal chemistry letters · 2015Article
- Redox control of the senescence regulator interleukin-1α and the secretory phenotype.The Journal of biological chemistry · 2013Article
- The role of HSPA12B in regulating neuronal apoptosis.Neurochemical research · 2013Article
- Use of an adult rat retinal explant model for screening of potential retinal ganglion cell neuroprotective therapies.Investigative ophthalmology & visual science · 2011Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cell-based approaches are a promising therapeutic strategy for treating injuries to the nervous system, but the optimal means to promote neurite extension and direct cellular behavior are unclear. Previous studies have examined the behavior of neural-like cells in ambient air (21% oxygen tension), yet these conditions are not representative of the physiological oxygen microenvironment of neural tissues. We hypothesized that neuronal differentiation of a model neural cell line (PC12) could be controlled by modulating local oxygen tension. Compared to ambient conditions, PC12 cells cultured in reduced oxygen exhibited significant increases in neurite extension and total neurite length, with 4% oxygen yielding the highest levels of both indicators. We confirmed neurite extension was mediated through oxygen-responsive mechanisms using small molecules that promote or inhibit HIF-1alpha stabilization. The hypoxic target gene Vegf was implicated as a neurotrophic factor, as neurite formation at 21% oxygen was mimicked with exogenous VEGF, and a VEGF-neutralizing antibody attenuated neurite formation under reduced oxygen conditions. These findings demonstrate that behavior of neural-like cells is driven by the oxygen microenvironment via VEGF function, and suggest promising approaches for future applications in neural repair.
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