| pubmed-article:10939628 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:10939628 | lifeskim:mentions | umls-concept:C0086418 | lld:lifeskim |
| pubmed-article:10939628 | lifeskim:mentions | umls-concept:C0035820 | lld:lifeskim |
| pubmed-article:10939628 | lifeskim:mentions | umls-concept:C0079281 | lld:lifeskim |
| pubmed-article:10939628 | lifeskim:mentions | umls-concept:C0225336 | lld:lifeskim |
| pubmed-article:10939628 | lifeskim:mentions | umls-concept:C0009148 | lld:lifeskim |
| pubmed-article:10939628 | lifeskim:mentions | umls-concept:C0242184 | lld:lifeskim |
| pubmed-article:10939628 | lifeskim:mentions | umls-concept:C0017262 | lld:lifeskim |
| pubmed-article:10939628 | lifeskim:mentions | umls-concept:C0851285 | lld:lifeskim |
| pubmed-article:10939628 | lifeskim:mentions | umls-concept:C0013879 | lld:lifeskim |
| pubmed-article:10939628 | pubmed:issue | 1-2 | lld:pubmed |
| pubmed-article:10939628 | pubmed:dateCreated | 2000-11-15 | lld:pubmed |
| pubmed-article:10939628 | pubmed:abstractText | Endothelin-1 (Et-1) is a vasoconstrictor peptide that plays an important role in the pathophysiology of hypertension, myocardial ischemia, and other diseases. We examined the mechanism of regulation the Et-1 mRNA expression in human microvascular endothelial cells (HMEC-1) in response to hypoxia and cobalt. To determine whether the 5'-flanking region of Et-1 gene mediate transcriptional responses to cellular hypoxia, we constructed reporter plasmids in which Et-1 5'-flanking sequences of Et-1 gene were fused to luciferase coding sequences. Constructs, which contain native Et-1 sequence 5'-AACGTGCA-3', located between -118 and -125 in the opposite orientation as the transcriptional unit, mediate transcriptional response to hypoxia and cobalt. This responsiveness was inhibited by genistein, a tyrosine kinase selective inhibitor. Both hypoxia and cobalt induced binding of HIF-1 (hypoxia inducible-1 factor) to this Et-1 hypoxia responsive element in gel shift assays. Mutation in this sequence eliminated both the hypoxia-induced HIF-1 binding and luciferase expression. Using the supershift assay we have shown that this hypoxia responsive element binds HIF-1alpha and HIF-1beta proteins. Interestingly, genistein only slightly affected HIF-1 binding. These results indicate that the Et-1 gene contains HIF-1 binding hypoxia responsive elements which mediate transcriptional responses to hypoxia and cobalt in microvascular endothelial cells. Genistein appears to inhibit this response by affecting the transcriptional activity of the HIF-1 complex, without significantly affecting its DNA-binding properties. | lld:pubmed |
| pubmed-article:10939628 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:10939628 | pubmed:language | eng | lld:pubmed |
| pubmed-article:10939628 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:10939628 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:10939628 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:10939628 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:10939628 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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| pubmed-article:10939628 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:10939628 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:10939628 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:10939628 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:10939628 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:10939628 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:10939628 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:10939628 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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| pubmed-article:10939628 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:10939628 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:10939628 | pubmed:month | May | lld:pubmed |
| pubmed-article:10939628 | pubmed:issn | 0300-8177 | lld:pubmed |
| pubmed-article:10939628 | pubmed:author | pubmed-author:CaroJJ | lld:pubmed |
| pubmed-article:10939628 | pubmed:author | pubmed-author:MinchenkoAA | lld:pubmed |
| pubmed-article:10939628 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:10939628 | pubmed:volume | 208 | lld:pubmed |
| pubmed-article:10939628 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:10939628 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:10939628 | pubmed:pagination | 53-62 | lld:pubmed |
| pubmed-article:10939628 | pubmed:dateRevised | 2007-11-14 | lld:pubmed |
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| pubmed-article:10939628 | pubmed:meshHeading | pubmed-meshheading:10939628... | lld:pubmed |
| pubmed-article:10939628 | pubmed:year | 2000 | lld:pubmed |
| pubmed-article:10939628 | pubmed:articleTitle | Regulation of endothelin-1 gene expression in human microvascular endothelial cells by hypoxia and cobalt: role of hypoxia responsive element. | lld:pubmed |
| pubmed-article:10939628 | pubmed:affiliation | Cardeza Foundation for Hematologic Research, Department of Medicine, Jefferson Medical College, Thomas Jefferson University, PA 19107, USA. | lld:pubmed |
| pubmed-article:10939628 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:10939628 | pubmed:publicationType | Research Support, U.S. Gov't, P.H.S. | lld:pubmed |
| pubmed-article:10939628 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
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