Evidence map›Paper›PMID 23342163›Full record

ArticlePloS one2013

High glucose induced alteration of SIRTs in endothelial cells causes rapid aging in a p300 and FOXO regulated pathway.

Rokhsana Mortuza, Shali Chen, Biao Feng, Subhrojit Sen, Subrata Chakrabarti

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

Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 112 papers.

0numbers the graph read from it
0cells of the map it votes in
112citing papers in PubMed
9.7field-weighted citation impact, top 1% 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

112 citing papers in PubMed, 205 citations in OpenAlex.

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52 more citing papers are in PubMed but not listed here.

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

5 authors at 1 institution in 1 country.

Rokhsana MortuzaDepartment of Pathology, Schulich School of Medicine & Dentistry, University of Western Ontario, London, Ontario, Canada.
Shali Chen
Biao Feng
Subhrojit Sen
Subrata Chakrabarti
Western University · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

In diabetes, some of the cellular changes are similar to aging. We hypothesized that hyperglycemia accelerates aging-like changes in the endothelial cells (ECs) and tissues leading to structural and functional damage. We investigated glucose-induced aging in 3 types of ECs using senescence associated β-gal (SA β-gal) staining and cell morphology. Alterations of sirtuins (SIRTs) and their downstream mediator FOXO and oxidative stress were investigated. Relationship of such alteration with histone acetylase (HAT) p300 was examined. Similar examinations were performed in tissues of diabetic animals. ECs in high glucose (HG) showed evidence of early senescence as demonstrated by increased SA β-gal positivity and reduced replicative capacities. These alterations were pronounced in microvascular ECs. They developed an irregular and hypertrophic phenotype. Such changes were associated with decreased SIRT (1-7) mRNA expressions. We also found that p300 and SIRT1 regulate each other in such process, as silencing one led to increase of the others' expression. Furthermore, HG caused reduction in FOXO1's DNA binding ability and antioxidant target gene expressions. Chemically induced increased SIRT1 activity and p300 knockdown corrected these abnormalities slowing aging-like changes. Diabetic animals showed increased cellular senescence in renal glomerulus and retinal blood vessels along with reduced SIRT1 mRNA expressions in these tissues. Data from this study demonstrated that hyperglycemia accelerates aging-like process in the vascular ECs and such process is mediated via downregulation of SIRT1, causing reduction of mitochondrial antioxidant enzyme in a p300 and FOXO1 mediated pathway.

Indexed as

Cellular SenescenceEndothelial CellsForkhead Box Protein O1Forkhead Transcription FactorsGlucoseMitochondrial ProteinsOxidative Stressp300-CBP-Associated Factorp300-CBP Transcription FactorsSirtuin 1Sirtuin 2Sirtuin 3SirtuinsForkhead Box Protein O1Forkhead Transcription FactorsFOXO1 protein, humanGlucoseMitochondrial Proteinsp300-CBP-Associated Factorp300-CBP Transcription FactorsSIRT1 protein, humanSIRT2 protein, humanSIRT3 protein, humanSIRT4 protein, humanSIRT5 protein, humanSIRT6 protein, humanSirtuin 1Sirtuin 2Sirtuin 3Sirtuins

Identifiers

PMID23342163
PMCPMC3546959
OpenAlexW2013636493

What OpenQuestion holds

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LicenceCC BY
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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.