Source:http://linkedlifedata.com/resource/pubmed/id/15557337
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
5
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| pubmed:dateCreated |
2005-2-7
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| pubmed:abstractText |
Hypoxia-inducible factor-1 (HIF-1) is a transcriptional activator involved in adaptation to hypoxic stress. Previous studies from our laboratory demonstrated that pharmacological activators of HIF-1 (e.g. deferoxamine, cobalt chloride) could also protect cultured primary neurons or an immortalized hippocampal neuroblast line (HT22) from oxidative stress-induced death. However, whether HIF-1 activation is sufficient to abrogate neuronal death resulting from oxidative stress or other hypoxia-independent death inducers remains unclear. To address this question we utilized a HIF-1alpha fusion protein that partially lacks the domain required for oxygen-dependent degradation of HIF-1alpha and that has a VP16 transcriptional activation domain from herpes simplex virus. HT22 cells were infected with a retrovirus encoding either the HIF-1alpha-VP16 fusion protein or the activation domain of the VP16 protein alone as a control. Expression of HIF-1alpha-VP16, but not VP16 alone, increased luciferase activity driven by a canonical hypoxia response element, increased mRNA of established HIF-1 target genes, and increased activity of one of these HIF-1 target genes. Unexpectedly, enhanced HIF-1 activity in HT22 cells enhanced sensitivity to oxidative death induced by glutathione depletion. Accordingly, suppression of HIF-1alpha expression using RNA interference prevented oxidative death. By contrast, HIF-1alpha-VP16-expressing HT22 cells were more resistant to DNA damage (induced by camptothecin) or endoplasmic reticulum stress (induced by thapsigargin and tunicamycin) than were VP16-expressing cells, and suppression of HIF-1alpha expression using RNA interference rendered HT22 cells more sensitive to death induced by DNA damage or endoplasmic reticulum stress. Together, these data demonstrate that HIF-1 can mediate prodeath or prosurvival responses in the same cell type depending on the injury stimulus.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Anti-Bacterial Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Camptothecin,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Herpes Simplex Virus Protein Vmw65,
http://linkedlifedata.com/resource/pubmed/chemical/Hypoxia-Inducible Factor 1, alpha...,
http://linkedlifedata.com/resource/pubmed/chemical/Oxygen,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Thapsigargin,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Tunicamycin
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| pubmed:status |
MEDLINE
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| pubmed:month |
Feb
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| pubmed:issn |
0021-9258
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:day |
4
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| pubmed:volume |
280
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
3996-4003
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| pubmed:dateRevised |
2007-11-14
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| pubmed:meshHeading |
pubmed-meshheading:15557337-Animals,
pubmed-meshheading:15557337-Anti-Bacterial Agents,
pubmed-meshheading:15557337-Camptothecin,
pubmed-meshheading:15557337-Cell Death,
pubmed-meshheading:15557337-Cell Line,
pubmed-meshheading:15557337-Cell Survival,
pubmed-meshheading:15557337-DNA Damage,
pubmed-meshheading:15557337-Enzyme Inhibitors,
pubmed-meshheading:15557337-Herpes Simplex Virus Protein Vmw65,
pubmed-meshheading:15557337-Hippocampus,
pubmed-meshheading:15557337-Hypoxia-Inducible Factor 1, alpha Subunit,
pubmed-meshheading:15557337-Mice,
pubmed-meshheading:15557337-Neurons,
pubmed-meshheading:15557337-Oxygen,
pubmed-meshheading:15557337-RNA, Small Interfering,
pubmed-meshheading:15557337-Recombinant Fusion Proteins,
pubmed-meshheading:15557337-Thapsigargin,
pubmed-meshheading:15557337-Transcription Factors,
pubmed-meshheading:15557337-Tunicamycin
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| pubmed:year |
2005
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| pubmed:articleTitle |
Prosurvival and prodeath effects of hypoxia-inducible factor-1alpha stabilization in a murine hippocampal cell line.
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| pubmed:affiliation |
Department of Neurology and Program in Neuroscience, Harvard Medical School, Boston, Massachusetts 02115, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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