Evidence map›Paper›PMID 23139272›Full record

ArticleInvestigative ophthalmology & visual science2012

Age-related susceptibility to apoptosis in human retinal pigment epithelial cells is triggered by disruption of p53-Mdm2 association.

Sujoy Bhattacharya, Edward Chaum, Dianna A Johnson, Leonard R Johnson

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Investigative ophthalmology & visual science, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed
6.1field-weighted citation impact, top 4% 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

37 citing papers in PubMed, 73 citations in OpenAlex.

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  20. Relevance of the p53-MDM2 axis to aging.Cell death and differentiation · 2018
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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

4 authors at 1 institution in 1 country.

Sujoy BhattacharyaDepartment of Physiology, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA. sbhatta3@uthsc.edu
Edward Chaum
Dianna A Johnson
Leonard R Johnson
University of Tennessee Health Science Center · US

Funding

GI HORMONES AND OTHER FACTORS ON GROWTH OF GI MUCOSAR37DK016505 · NIDDK · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI TIGYI, GABOR J · 1988 to 2014
$4.8M
GI HORMONES AND OTHER FACTORS ON GROWTH OF GI MUCOSAR01DK016505 · NIDDK · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI JOHNSON, LEONARD R. · 1986 to 2004
$2.0M
NIDDK NIH HHS DK-16505NIDDK NIH HHS R01 DK016505NIDDK NIH HHS R37 DK016505
6 · The paper itself

Abstract

purposeRelatively little is known about the contribution of p53/Mdm2 pathway in apoptosis of retinal pigment epithelial (RPE) cells or its possible link to dysfunction of aging RPE or to related blinding disorders such as age-related macular degeneration (AMD).

methodsAge-associated changes in p53 activation were evaluated in primary RPE cultures from human donor eyes of various ages. Apoptosis was evaluated by activation of caspases and DNA fragmentation. Gene-specific small interfering RNA was used to knock down expression of p53.

resultsWe observed that the basal rate of p53-dependent apoptosis increased in an age-dependent manner in human RPE. The age-dependent increase in apoptosis was linked to alterations in several aspects of the p53 pathway. p53 phosphorylation Ser15 was increased through the stimulation of ATM-Ser1981. p53 acetylation Lys379 was increased through the inhibition of SIRT1/2. These two posttranslational modifications of p53 blocked the sequestration of p53 by Mdm2, thus resulting in an increase in free p53 and of p53 stimulation of apoptosis through increased expression of PUMA (p53 upregulated modulator of apoptosis) and activation of caspase-3. Aged RPE also had reduced expression of antiapoptotic Bcl-2, which contributed to the increase in apoptosis. Of particular interest in these studies was that pharmacologic treatments to block p53 phosphorylation, acetylation, or expression were able to protect RPE cells from apoptosis.

conclusionsOur studies suggest that aging in the RPE leads to alterations of specific checkpoints in the apoptotic pathway, which may represent important molecular targets for the treatment of RPE-related aging disorders such as AMD.

Indexed as

AcetylationAdultAgedAged, 80 and overAgingApoptosisApoptosis Regulatory ProteinsBenzamidesBlotting, WesternCaspase 3Cell ProliferationCells, CulturedDisease SusceptibilityDNA FragmentationEnzyme-Linked Immunosorbent AssayFluorescent Antibody Technique, IndirectApoptosis Regulatory ProteinsBBC3 protein, humanBenzamidesCASP3 protein, humanCaspase 3ImidazolesMDM2 protein, humanNaphtholsnutlin 3PiperazinesProto-Oncogene ProteinsProto-Oncogene Proteins c-mdm2RNA, Small InterferingSIRT1 protein, humanSIRT2 protein, humansirtinolSirtuin 1Sirtuin 2Tumor Suppressor Protein p53

Identifiers

PMID23139272
PMCPMC4113331
OpenAlexW2077203470

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.