Evidence map›Paper›PMID 27367846›Full record

ArticleFree radical research2016

Hypo-CpG methylation controls PTEN expression and cell apoptosis in irradiated lung.

Xiuwu Zhang, Caroline Hadley, Isabel L Jackson, Yi Zhang, Angel Zhang, Ivan Spasojevic, Ines Batinic Haberle, Zeljko Vujaskovic

Abstract read
In one paragraph

Article in Free radical research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
1.0field-weighted citation impact, top 21% of its field
1 · What the graph read from it

What it found

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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

9 citing papers in PubMed, 16 citations in OpenAlex.

  1. Review
  2. Article
  3. [Progression of Anti-oxygen Therapy in Radiation-Induced Lung Injury].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2019
    Review
  4. Article
  5. Review
  6. Adiponectin inhibits hepatic stellate cell activation by targeting the PTEN/AKT pathway.Biochimica et biophysica acta. Molecular basis of disease · 2018
    Article
  7. Article
  8. NADPH Oxidase Activation Contributes to Heavy Ion Irradiation-Induced Cell Death.Dose-response : a publication of International Hormesis Society
    Article
  9. Article
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

8 authors at 3 institutions in 1 country.

Xiuwu Zhanga Division of Translational Radiation Sciences, Department of Radiation Oncology , University of Maryland, School of Medicine , Baltimore , MD , USA ;
Caroline Hadleyb Baylor University School of Medicine , Houston , TX , USA ;
Isabel L Jacksona Division of Translational Radiation Sciences, Department of Radiation Oncology , University of Maryland, School of Medicine , Baltimore , MD , USA ;
Yi Zhanga Division of Translational Radiation Sciences, Department of Radiation Oncology , University of Maryland, School of Medicine , Baltimore , MD , USA ;
Angel Zhanga Division of Translational Radiation Sciences, Department of Radiation Oncology , University of Maryland, School of Medicine , Baltimore , MD , USA ;
Ivan Spasojevicc Department of Radiation Oncology , Duke University Medical Center , Durham , NC , USA.
Ines Batinic Haberlea Division of Translational Radiation Sciences, Department of Radiation Oncology , University of Maryland, School of Medicine , Baltimore , MD , USA ;
Zeljko Vujaskovica Division of Translational Radiation Sciences, Department of Radiation Oncology , University of Maryland, School of Medicine , Baltimore , MD , USA ;
University of Maryland, Baltimore · USDuke Medical Center · USBaylor School · US

Funding

Somatostatin analogues as countermeasures against intestinal radiation toxicityU19AI067798 · NIAID · DUKE UNIVERSITY · PI DOAN, PHUONG LINH · 2005 to 2024
$82.1M
NIAID NIH HHS U19 AI067798
6 · The paper itself

Abstract

purposeThe current study was designed to address our hypothesis that oxidative stress secondary to the ionizing event upregulates phosphatase and tensin homolog (PTEN) mRNA and protein in the lungs of C57BL/6J mice through oxidative DNA damage resulting in CpG hypomethylation in the PTEN promoter.

methodsFibrosis-prone C57BL/6J mice were exposed to 0 or 15 Gy of 320 kVp X-rays to the whole thorax. Lung tissue was serially harvested at time points between one day and six months postirradiation. Tissue levels of PTEN mRNA, total protein, and phosphorylated PTEN, as well as CpG methylation of the PTEN promoter, expression of DNA methyltransferases 1 (Dnmt1) and 3a (Dnmt3a), NADPH oxidase 4 (Nox4) protein expression, and DNA damage levels were measured. The induction of DNA damage and global methylation changes were also examined in hydrogen peroxide (H2O2)-treated human umbilical vein endothelial cells (HUVECs) and human bronchial epithelial cells in vitro.

resultsThese experiments demonstrate that PTEN mRNA and protein, Nox4 protein, and DNA damage levels increase continuously from one day to six months following radiation exposure. Elevated PTEN transcription and translation are likely the result of the observed decrease in CpG methylation of the PTEN promoter region. This finding is not consistent with the observed increase in Dnmt1 and Dnmt3a protein expression, implicating an alternative mechanism as the driving force behind hypomethylation. In vitro results provide evidence that H2O2 can induce DNA damage and affect DNA methylation status. The Mn porphyrin-based superoxide dismutase (SOD) mimic MnTnHEx-2-PyP(5+ )exhibited partial rescue from radiation-induced hypomethylation.

conclusionsTaken together, these data suggest that reactive oxygen species (ROS)-induced DNA damage results in hypomethylation of the PTEN promoter, upregulation of PTEN mRNA and protein, and a subsequent increase in apoptosis in irradiated lung tissue.

Indexed as

CpG IslandsDNA MethylationAnimalsApoptosisDNA-Cytosine MethylasesDNA DamageFemaleHumansHuman Umbilical Vein Endothelial CellsLungMiceMice, Inbred C57BLPhosphorylationPromoter Regions, GeneticPTEN PhosphohydrolaseRNA, MessengerDNA-Cytosine MethylasesPTEN PhosphohydrolasePTEN protein, humanRNA, MessengerMethylationPTENradiation lung injurywhole thorax irradiation

Identifiers

PMID27367846
PMCPMC6121701
OpenAlexW2464137158

What OpenQuestion holds

Textmetadata
LicenceTDM
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.