Evidence map›Paper›PMID 25389371›Full record

ArticleScience signaling2014

Inflammatory stimuli induce inhibitory S-nitrosylation of the deacetylase SIRT1 to increase acetylation and activation of p53 and p65.

Shohei Shinozaki, Kyungho Chang, Michihiro Sakai, Nobuyuki Shimizu, Marina Yamada, Tomokazu Tanaka, Harumasa Nakazawa, Fumito Ichinose, Yoshitsugu Yamada, Akihito Ishigami and 7 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Science signaling, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
81citing papers in PubMed, 1 pooled it
6.7field-weighted citation impact, top 3% 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

81 citing papers in PubMed, 1 synthesis or guideline pooled it, 136 citations in OpenAlex.

  1. A systematic review of p53 regulation of oxidative stress in skeletal muscle.Redox report : communications in free radical research · 2018
    Pooled it
  2. Review
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  4. Article
  5. Thermogenic Adipose ADH5 Counteracts Age-related Metabolic Decline.bioRxiv : the preprint server for biology · 2025
    Article
  6. International journal of molecular sciences · 2025
    Article
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21 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

17 authors at 3 institutions in 2 countries.

Shohei ShinozakiDepartment of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Shriners Hospitals for Children, Harvard Medical School, Charlestown, MA 02129, USA. Department of Geriatrics and Vascular Medicine, Tokyo Medical and Dental University Graduate School, Tokyo 113-8519, Japan.
Kyungho ChangDepartment of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Shriners Hospitals for Children, Harvard Medical School, Charlestown, MA 02129, USA. Department of Anesthesiology and Pain Relief Center, Graduate School of Medicine, University of Tokyo, Tokyo 113-8655, Japan.
Michihiro SakaiDepartment of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Shriners Hospitals for Children, Harvard Medical School, Charlestown, MA 02129, USA.
Nobuyuki ShimizuDepartment of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Shriners Hospitals for Children, Harvard Medical School, Charlestown, MA 02129, USA.
Marina YamadaDepartment of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Shriners Hospitals for Children, Harvard Medical School, Charlestown, MA 02129, USA.
Tomokazu TanakaDepartment of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Shriners Hospitals for Children, Harvard Medical School, Charlestown, MA 02129, USA.
Harumasa NakazawaDepartment of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Shriners Hospitals for Children, Harvard Medical School, Charlestown, MA 02129, USA.
Fumito IchinoseDepartment of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Shriners Hospitals for Children, Harvard Medical School, Charlestown, MA 02129, USA.
Yoshitsugu YamadaDepartment of Anesthesiology and Pain Relief Center, Graduate School of Medicine, University of Tokyo, Tokyo 113-8655, Japan.
Akihito IshigamiTokyo Metropolitan Institute of Gerontology, Tokyo 173-0015, Japan.
Hideki ItoTokyo Metropolitan Institute of Gerontology, Tokyo 173-0015, Japan.
Yasuyoshi OuchiDepartment of Geriatric Medicine, Graduate School of Medicine, University of Tokyo, Tokyo 113-8655, Japan. Federation of National Public Service Personnel Mutual Aid Associations Toranomon Hospital, Tokyo 105-0001, Japan.
Marlene E StarrDepartment of Surgery, University of Kentucky College of Medicine, Lexington, KY 40536, USA.
Hiroshi SaitoDepartment of Surgery, University of Kentucky College of Medicine, Lexington, KY 40536, USA.
Kentaro ShimokadoDepartment of Geriatrics and Vascular Medicine, Tokyo Medical and Dental University Graduate School, Tokyo 113-8519, Japan.
Jonathan S StamlerInstitute for Transformative Molecular Medicine and Harrington Discovery Institute, Case Western Reserve University and University Hospital, Cleveland, OH 44106, USA.
Masao KanekiDepartment of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Shriners Hospitals for Children, Harvard Medical School, Charlestown, MA 02129, USA. mkaneki@helix.mgh.harvard.edu.
Tokyo Metropolitan Institute of Gerontology · JPUniversity of Kentucky · USThe University of Tokyo · JP

Funding

WOUND HEALINGP50GM021700 · NIGMS · MASSACHUSETTS GENERAL HOSPITAL · PI MARTYN, JEEVENDRA · 1985 to 2017
$27.2M
Regulation of Beta-Adrenergic Receptor Signaling by S-NitrosylationP01HL075443 · NHLBI · DUKE UNIVERSITY · PI STAMLER, JONATHAN S. · 2004 to 2019
$26.1M
Inducible Nitric Oxide Synthase and Insulin ResistanceR01DK058127 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI KANEKI, MASAO · 2002 to 2009
$2.1M
The Role of Adipose Tissue in Age-dependent Sensitivity to Critical IllnessR01AG039732 · NIA · UNIVERSITY OF KENTUCKY · PI SAITO, HIROSHI · 2011 to 2015
$1.5M
Identification of Novel DenitrosylasesR01GM099921 · NIGMS · CASE WESTERN RESERVE UNIVERSITY · PI STAMLER, JONATHAN S. · 2013 to 2016
$1.4M
NHLBI NIH HHS 5P01-HL-075443-08NHLBI NIH HHS P01 HL075443NIA NIH HHS R01 AG039732NIA NIH HHS R01-AG-039732NIDDK NIH HHS R01 DK058127NIDDK NIH HHS R01-DK-058127NIGMS NIH HHS P50 GM021700NIGMS NIH HHS R01 GM099921NIGMS NIH HHS R01-GM-099921
6 · The paper itself

Abstract

Inflammation increases the abundance of inducible nitric oxide synthase (iNOS), leading to enhanced production of nitric oxide (NO), which can modify proteins by S-nitrosylation. Enhanced NO production increases the activities of the transcription factors p53 and nuclear factor κB (NF-κB) in several models of disease-associated inflammation. S-nitrosylation inhibits the activity of the protein deacetylase SIRT1. SIRT1 limits apoptosis and inflammation by deacetylating p53 and p65 (also known as RelA), a subunit of NF-κB. We showed in multiple cultured mammalian cell lines that NO donors or inflammatory stimuli induced S-nitrosylation of SIRT1 within CXXC motifs, which inhibited SIRT1 by disrupting its ability to bind zinc. Inhibition of SIRT1 reduced deacetylation and promoted activation of p53 and p65, leading to apoptosis and increased expression of proinflammatory genes. In rodent models of systemic inflammation, Parkinson's disease, or aging-related muscular atrophy, S-nitrosylation of SIRT1 correlated with increased acetylation of p53 and p65 and activation of p53 and NF-κB target genes, suggesting that S-nitrosylation of SIRT1 may represent a proinflammatory switch common to many diseases and aging.

Indexed as

InflammationAcetylationAmino Acid MotifsAmino Acid SequenceAnimalsApoptosisChlorocebus aethiopsCOS CellsDisease Models, AnimalHumansMaleMiceMice, Inbred C57BLMolecular Sequence DataNF-kappa BNitrogenNF-kappa BNitrogenRELA protein, humanRela protein, mouseRela protein, ratSIRT1 protein, humanSirt1 protein, mouseSirt1 protein, ratSirtuin 1TP53 protein, humanTranscription Factor RelATumor Suppressor Protein p53

Identifiers

PMID25389371
PMCPMC4340581
OpenAlexW2160600666

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.