Evidence map›Paper›PMID 10939628›Full record

ArticleMolecular and cellular biochemistry2000

Regulation of endothelin-1 gene expression in human microvascular endothelial cells by hypoxia and cobalt: role of hypoxia responsive element.

A Minchenko, J Caro

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In one paragraph

Article in Molecular and cellular biochemistry, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed, 1 pooled it
2.6field-weighted citation impact, top 10% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

34 citing papers in PubMed, 1 synthesis or guideline pooled it, 120 citations in OpenAlex.

  1. Pooled it
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  9. Strategies forBiomedical reports · 2023
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  11. TheInternational journal of environmental research and public health · 2022
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

2 authors at 1 institution in 1 country.

A MinchenkoCardeza Foundation for Hematologic Research, Department of Medicine, Jefferson Medical College, Thomas Jefferson University, PA 19107, USA.
J Caro
Thomas Jefferson University · US

Funding

RENAL ERYTHROPOIETIN BIOGENESISR01DK034642 · NIDDK · THOMAS JEFFERSON UNIVERSITY · PI CARO, JAIME · 1986 to 1996
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NIDDK NIH HHS DK34642
6 · The paper itself

Abstract

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.

Indexed as

Cell HypoxiaGene Expression RegulationCell LineCobaltDNA-Binding ProteinsElectrophoresis, Polyacrylamide GelEndothelin-1Endothelium, VascularEnzyme InhibitorsGenes, ReporterGenisteinHumansHypoxia-Inducible Factor 1Hypoxia-Inducible Factor 1, alpha SubunitLuciferasesNuclear ProteinsCobaltDNA-Binding ProteinsEndothelin-1Enzyme InhibitorsGenisteinHIF1A protein, humanHypoxia-Inducible Factor 1Hypoxia-Inducible Factor 1, alpha SubunitLuciferasesNuclear ProteinsProtein PrecursorsRecombinant Fusion ProteinsRNA, MessengerTranscription Factors

Identifiers

PMID10939628
OpenAlexW334389957

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.