Evidence map›Paper›PMID 27585400›Full record

ArticleAmerican journal of respiratory cell and molecular biology2017

2-O, 3-O Desulfated Heparin Blocks High Mobility Group Box 1 Release by Inhibition of p300 Acetyltransferase Activity.

Shuo Zheng, Apparao B Kummarapurugu, Daniel K Afosah, Nehru Viji Sankaranarayanan, Rio S Boothello, Umesh R Desai, Thomas Kennedy, Judith A Voynow

Open access · greenAbstract read
In one paragraph

Article in American journal of respiratory cell and molecular biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
2.6field-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

20 citing papers in PubMed, 31 citations in OpenAlex.

  1. Review
  2. Article
  3. Glycosaminoglycans as Polyelectrolytes: Charge, Interactions, and Applications.Chembiochem : a European journal of chemical biology · 2025
    Review
  4. Article
  5. Review
  6. Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. Article
  12. Review
  13. Non-Anticoagulant Heparins as Heparanase Inhibitors.Advances in experimental medicine and biology · 2020
    Review
  14. Review
  15. Article
  16. Review
  17. Review
  18. Article
  19. Mechanisms and Targeted Therapies for Pseudomonas aeruginosa Lung Infection.American journal of respiratory and critical care medicine · 2018
    Review
  20. Review
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.

Shuo Zheng1 Department of Pediatrics and.
Apparao B Kummarapurugu1 Department of Pediatrics and.
Daniel K Afosah2 Medicinal Chemistry and Institute for Structural Biology, Drug Discovery and Development, Virginia Commonwealth University, Richmond, Virginia; and.
Nehru Viji Sankaranarayanan2 Medicinal Chemistry and Institute for Structural Biology, Drug Discovery and Development, Virginia Commonwealth University, Richmond, Virginia; and.
Rio S Boothello2 Medicinal Chemistry and Institute for Structural Biology, Drug Discovery and Development, Virginia Commonwealth University, Richmond, Virginia; and.
Umesh R Desai2 Medicinal Chemistry and Institute for Structural Biology, Drug Discovery and Development, Virginia Commonwealth University, Richmond, Virginia; and.
Thomas Kennedy3 Wake Forest University, Winston-Salem, North Carolina.
Judith A Voynow1 Department of Pediatrics and.
Virginia Commonwealth University · USPediatrics and Genetics · USWake Forest University · US

Funding

Therapeutic assessment of synthetic heparin sulfates in transplantation modelsP01HL107152 · NHLBI · VIRGINIA COMMONWEALTH UNIVERSITY · PI DESAI, UMESH RAMANLAL · 2011 to 2017
$15.8M
High Performance Computing Cluster for Biomedical Research at VCUS10RR027411 · NCRR · VIRGINIA COMMONWEALTH UNIVERSITY · PI CUI, MENG · 2010 to 2010
$417k
NCRR NIH HHS S10 RR027411NHLBI NIH HHS P01 HL107152
6 · The paper itself

Abstract

High mobility group box 1 (HMGB1) is an alarmin released from macrophages after infection or inflammation and is a biomarker of lung disease progression in patients with cystic fibrosis. We reported that 2-O, 3-O desulfated heparin (ODSH) inhibits the release of HMGB1 from murine macrophages triggered by neutrophil elastase both in vivo and in vitro. HMGB1 shuttles between the nucleus and the cytoplasm. When acetylated at lysine residues in the nuclear localization signal domains, HMGB1 is sequestered in the cytoplasm and is fated for secretion. In this study, we investigated the mechanism by which ODSH blocks HMGB1 secretion. We tested whether ODSH inhibits the activity of p300, a histone acetyltransferase that has been linked to HMGB1 acetylation and release. ODSH inhibited both neutrophil elastase and LPS-triggered HMGB1 release from the murine macrophage cell line RAW264.7 in a concentration-dependent manner. Fluorescein-labeled ODSH was taken up by RAW264.7 cells into the cytoplasm as well as the nucleus, suggesting an intracellular site of action of ODSH for blocking HMGB1 release. ODSH inhibited RAW264.7 cell nuclear extract, human macrophage nuclear extract, and recombinant p300 HAT activity in vitro, resulting in the failure to acetylate HMGB1. In silico molecular modeling predicted that of the numerous possible ODSH sequences, a small number preferentially recognizes a specific binding site on p300. Fluorescence binding studies showed that ODSH bound p300 tightly (dissociation constant ∼1 nM) in a highly cooperative manner. These results suggest that ODSH inhibited HMGB1 release, at least in part, by direct molecular inhibition of p300 HAT activity.

Indexed as

AcetylationAnimalsCell NucleusComputer SimulationHeparinHMGB1 ProteinHumansLeukocyte ElastaseLipopolysaccharidesLysineMiceModels, Molecularp300-CBP-Associated Factorp300-CBP Transcription FactorsRAW 264.7 CellsSpectrometry, FluorescenceHeparinheparin, O-desulfatedHMGB1 ProteinLeukocyte ElastaseLipopolysaccharidesLysinep300-CBP-Associated Factorp300-CBP Transcription Factorsheparinhigh mobility group box 1p300

Identifiers

PMID27585400
PMCPMC5248960
OpenAlexW2508422351

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.