Source:http://linkedlifedata.com/resource/pubmed/id/19384570
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
4
|
| pubmed:dateCreated |
2009-4-22
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| pubmed:abstractText |
Hypoxia-inducible factor-1 (HIF-1) plays an important role in neural progenitor cell (NPC) propagation and dopaminergic differentiation. In the presence of oxygen and iron, hypoxia-inducible factor 1 alpha (HIF-1alpha) is rapidly degraded via the prolyl hydroxylase (PHD)/VHL pathway. In addition to hypoxia, various non-hypoxic stimuli can stabilize HIF-1alpha in NPCs and influence the transcription of HIF-regulated genes. Here, we investigate various hypoxia mimetics: deferoxamine (DFO), ciclopirox olamine (CPX), dimethyloxallyl glycine (DMOG), a novel HIF-PHD inhibitor (FG-4497) and cobalt chloride (CoCl(2)) with respect to their ability to enhance in vitro proliferation, neurogenesis and dopaminergic differentiation of human fetal mesencephalic NPCs (hmNPCs) in ambient oxygen (21%). Although able to stabilize HIF-1alpha, iron chelators (DFO and CPX) and DMOG were toxic to hmNPCs. CoCl(2) was beneficial only towards neuronal and dopaminergic differentiation, while FG-4497 enhanced proliferation, neurogenesis and dopaminergic differentiation of hmNPCs. Both CoCl(2) and FG-4497 were protective to human dopaminergic neurons. Finally, exposure to hyperbaric oxygen (HBO) also stabilized HIF-1alpha in hmNPCs and induced neurogenesis in vitro. These findings suggest that several HIF stabilizing agents or conditions can rescue impaired neurons and promote neurogenesis in vitro.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Actins,
http://linkedlifedata.com/resource/pubmed/chemical/Antifungal Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Cobalt,
http://linkedlifedata.com/resource/pubmed/chemical/Deferoxamine,
http://linkedlifedata.com/resource/pubmed/chemical/Hypoxia-Inducible Factor 1, alpha...,
http://linkedlifedata.com/resource/pubmed/chemical/Nerve Tissue Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Pyridones,
http://linkedlifedata.com/resource/pubmed/chemical/Siderophores,
http://linkedlifedata.com/resource/pubmed/chemical/ciclopirox,
http://linkedlifedata.com/resource/pubmed/chemical/cobaltous chloride
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
May
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| pubmed:issn |
1476-3524
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| pubmed:author | |
| pubmed:issnType |
Electronic
|
| pubmed:volume |
15
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
367-80
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| pubmed:meshHeading |
pubmed-meshheading:19384570-Actins,
pubmed-meshheading:19384570-Analysis of Variance,
pubmed-meshheading:19384570-Antifungal Agents,
pubmed-meshheading:19384570-Cell Cycle,
pubmed-meshheading:19384570-Cell Death,
pubmed-meshheading:19384570-Cell Differentiation,
pubmed-meshheading:19384570-Cell Line, Transformed,
pubmed-meshheading:19384570-Cell Proliferation,
pubmed-meshheading:19384570-Cell Survival,
pubmed-meshheading:19384570-Cobalt,
pubmed-meshheading:19384570-Deferoxamine,
pubmed-meshheading:19384570-Dose-Response Relationship, Drug,
pubmed-meshheading:19384570-Embryonic Stem Cells,
pubmed-meshheading:19384570-Fetus,
pubmed-meshheading:19384570-Humans,
pubmed-meshheading:19384570-Hyperbaric Oxygenation,
pubmed-meshheading:19384570-Hypoxia-Inducible Factor 1, alpha Subunit,
pubmed-meshheading:19384570-Mesencephalon,
pubmed-meshheading:19384570-Nerve Tissue Proteins,
pubmed-meshheading:19384570-Pyridones,
pubmed-meshheading:19384570-Siderophores
|
| pubmed:year |
2009
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| pubmed:articleTitle |
Non-hypoxic stabilization of hypoxia-inducible factor alpha (HIF-alpha): relevance in neural progenitor/stem cells.
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| pubmed:affiliation |
Translational Centre for Regenerative Medicine-Leipzig (TRM-Leipzig), University of Leipzig, Philipp-Rosenthal-Strasse 55, 04103, Leipzig, Germany. jmilosevic@trm.uni-leipzig.de
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|