Evidence map›Paper›PMID 22844079›Full record

ArticleMutagenesis2012

Angiotensin II induces DNA damage via AT1 receptor and NADPH oxidase isoform Nox4.

Gholamreza Fazeli, Helga Stopper, Reinhard Schinzel, Chih-Wen Ni, Hanjoong Jo, Nicole Schupp

Open access · greenAbstract read
In one paragraph

Article in Mutagenesis, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
2.3field-weighted citation impact, top 11% 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

23 citing papers in PubMed, 58 citations in OpenAlex.

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  11. Update onCancers · 2020
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  16. Ca2+ -regulated lysosome fusion mediates angiotensin II-induced lipid raft clustering in mesenteric endothelial cells.Hypertension research : official journal of the Japanese Society of Hypertension · 2016
    Article
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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

6 authors at 4 institutions in 2 countries.

Gholamreza FazeliInstitute of Pharmacology and Toxicology, Versbacher Str. 9, University of Würzburg, 97078 Würzburg, Germany.
Helga Stopper
Reinhard Schinzel
Chih-Wen Ni
Hanjoong Jo
Nicole Schupp
University of Würzburg · DEEmory University · USThe Wallace H. Coulter Department of Biomedical Engineering · USVasopharm (Germany) · DE

Funding

Shear and Oxidative Stress Regulate Endothelial Matrix MetalloproteinaseP01HL075209 · NHLBI · EMORY UNIVERSITY · PI GRIENDLING, KATHY K · 2004 to 2008
$7.5M
Reactive nitrogen species in shear-dependent signalingR01HL071014 · NHLBI · EMORY UNIVERSITY · PI JO, HANJOONG · 2002 to 2005
$1.2M
6 · The paper itself

Abstract

Epidemiological studies revealed increased renal cancer incidences and higher cancer mortalities in hypertensive individuals. Activation of the renin-angiotensin-aldosterone system leads to the formation of reactive oxygen species (ROS). In vitro, in renal cells, and ex vivo, in the isolated perfused mouse kidney, we could show DNA-damaging potential of angiotensin II (Ang II). Here, the pathway involved in the genotoxicity of Ang II was investigated. In kidney cell lines with properties of proximal tubulus cells, an activation of NADPH oxidase and the production of ROS, resulting in the formation of DNA strand breaks and micronuclei induction, was observed. This DNA damage was mediated by the Ang II type 1 receptor (AT1R), together with the G protein G ( α-q/11 ) . Subsequently, phospholipase C (PLC) was activated and intracellular calcium increased. Both calcium stores of the endoplasmic reticulum and extracellular calcium were involved in the genotoxicity of Ang II. Downstream, a role for protein kinase C (PKC) could be detected, because its inhibition hindered Ang II from damaging the cells. Although PKC was activated, no involvement of its known target, the NADPH oxidase isoform containing the Nox2 subunit, could be found, as tested by small-interfering RNA down-regulation. Responsible for the DNA-damaging activity of Ang II was the NADPH oxidase isoform containing the Nox4 subunit. In summary, in kidney cells the DNA-damaging activity of Ang II depends on an AT1R-mediated activation of NADPH oxidase via PLC, PKC and calcium signalling, with the NADPH subunit Nox4 playing a crucial role.

Indexed as

Angiotensin IIAnimalsCalciumCalcium SignalingCell LineDNA DamageDown-RegulationKidneyMaleMiceMice, Inbred C57BLNADPH Oxidase 4NADPH OxidasesProtein Kinase CReactive Oxygen SpeciesReceptor, Angiotensin, Type 1Angiotensin IICalciumNADPH Oxidase 4NADPH OxidasesNox4 protein, mouseProtein Kinase CReactive Oxygen SpeciesReceptor, Angiotensin, Type 1Type C Phospholipases

Identifiers

PMID22844079
PMCPMC6281047
OpenAlexW2133396367

What OpenQuestion holds

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Read underepoch 390

Registered trials

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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.