Source:http://linkedlifedata.com/resource/pubmed/id/11591789
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
8
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| pubmed:dateCreated |
2001-10-9
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| pubmed:abstractText |
The bone marrow (BM), which is the major site of immune cell development in the adult, responds to different stimuli such as inflammation and hemorrhagic shock. Substance P (SP) is the major peptide encoded by the immune/hemopoietic modulator gene, preprotachykinin-1 (PPT-I). Differential gene expression using a microarray showed that SP reduced hypoxia-inducible factor-1alpha (HIF-1alpha) mRNA levels in BM stroma. Because long-term hypoxia induced the expression of PPT-I in BM mononuclear cells, we used timeline studies to determine whether PPT-I is central to the biologic responses of BM stroma subjected to 30-min hypoxia (pO(2) = 35 mm Hg) followed by reoxygenation. HIF-1alpha mRNA and protein levels were increased up to 12 h. At this time, beta-PPT-I mRNA was detected with the release of SP at 16 h. SP release correlated with down-regulation of HIF-1alpha to baseline. A direct role for SP in HIF-1alpha expression was demonstrated as follows: 1) transient knockout of beta-PPT-I showed an increase in HIF-1alpha expression up to 48 h of reoxygenation; and 2) HIF-1alpha expression remained baseline during reoxygenation when stroma was subjected to hypoxia in the presence of SP. Reoxygenation activated the PPT-I promoter with concomitant nuclear translocation of HIF-1alpha that can bind to the respective consensus sequences within the PPT-I promoter. SP reversed active caspase-3, an indicator of apoptosis and erythropoiesis, to homeostasis level after reoxygenation of hypoxic stroma. The results show that during reoxgenation the PPT-I gene acts as a negative regulator on the expression of HIF-1alpha and active caspase-3 in BM stroma subjected to reoxygenation.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
AIM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/5' Untranslated Regions,
http://linkedlifedata.com/resource/pubmed/chemical/CASP3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Caspases,
http://linkedlifedata.com/resource/pubmed/chemical/HIF1A protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Hypoxia-Inducible Factor 1, alpha...,
http://linkedlifedata.com/resource/pubmed/chemical/Oxygen,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Precursors,
http://linkedlifedata.com/resource/pubmed/chemical/Substance P,
http://linkedlifedata.com/resource/pubmed/chemical/Tachykinins,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/preprotachykinin
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| pubmed:status |
MEDLINE
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| pubmed:month |
Oct
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| pubmed:issn |
0022-1767
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:day |
15
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| pubmed:volume |
167
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
4600-8
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| pubmed:dateRevised |
2008-11-21
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| pubmed:meshHeading |
pubmed-meshheading:11591789-5' Untranslated Regions,
pubmed-meshheading:11591789-Adult,
pubmed-meshheading:11591789-Bone Marrow,
pubmed-meshheading:11591789-Caspase 3,
pubmed-meshheading:11591789-Caspases,
pubmed-meshheading:11591789-Cell Hypoxia,
pubmed-meshheading:11591789-Enzyme Activation,
pubmed-meshheading:11591789-Gene Expression Regulation,
pubmed-meshheading:11591789-Hematopoiesis,
pubmed-meshheading:11591789-Humans,
pubmed-meshheading:11591789-Hypoxia-Inducible Factor 1, alpha Subunit,
pubmed-meshheading:11591789-Oxygen,
pubmed-meshheading:11591789-Promoter Regions, Genetic,
pubmed-meshheading:11591789-Protein Precursors,
pubmed-meshheading:11591789-Stromal Cells,
pubmed-meshheading:11591789-Substance P,
pubmed-meshheading:11591789-Tachykinins,
pubmed-meshheading:11591789-Transcription Factors
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| pubmed:year |
2001
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| pubmed:articleTitle |
Induction of hypoxia-inducible factor-1alpha and activation of caspase-3 in hypoxia-reoxygenated bone marrow stroma is negatively regulated by the delayed production of substance P.
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| pubmed:affiliation |
Department of Medicine, Trauma Division, University of Medicine and Dentistry of New Jersey, Newark, NJ 07103, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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