Evidence map›Paper›PMID 23447529›Full record

Trial reportThe Journal of biological chemistry2013

Real-time kinetics of high-mobility group box 1 (HMGB1) oxidation in extracellular fluids studied by in situ protein NMR spectroscopy.

Levani Zandarashvili, Debashish Sahu, Kwanbok Lee, Yong Sun Lee, Pomila Singh, Krishna Rajarathnam, Junji Iwahara

Open access · hybridAbstract readClinical Trial
In one paragraph

Trial report in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.

0numbers the graph read from it
0cells of the map it votes in
54citing papers in PubMed
3.0field-weighted citation impact, top 10% 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

54 citing papers in PubMed, 86 citations in OpenAlex.

  1. Modulation of HMGB1, PRF1, TRAIL, and M-CSF after TARGIT-IORT in breast-conserving surgery: defining a unique acute immune landscape.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
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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

7 authors at 1 institution in 1 country.

Levani ZandarashviliDepartment of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, Texas 77555-1068, USA.
Debashish Sahu
Kwanbok Lee
Yong Sun Lee
Pomila Singh
Krishna Rajarathnam
Junji Iwahara
The University of Texas Medical Branch at Galveston · US

Funding

UTMB CLINICAL AND TRANSLATIONAL SCIENCE AWARD: NASA BED REST STUDIESUL1RR029876 · NCRR · UNIVERSITY OF TEXAS MED BR GALVESTON · PI BRASIER, ALLAN R. · 2009 to 2011
$17.7M
Therapeutic assessment of synthetic heparin sulfates in transplantation modelsP01HL107152 · NHLBI · VIRGINIA COMMONWEALTH UNIVERSITY · PI DESAI, UMESH RAMANLAL · 2011 to 2017
$15.8M
UTMB Clinical and Translational Science AwardUL1TR000071 · NCATS · UNIVERSITY OF TEXAS MED BR GALVESTON · PI BRASIER, ALLAN R. · 2012 to 2014
$14.4M
Role of Annexin-II in growth factor/co-carcinogenic effects of progastrinR01CA097959 · NCI · UNIVERSITY OF TEXAS MEDICAL BR GALVESTON · PI SINGH, POMILA · 2003 to 2015
$3.7M
NCATS NIH HHS 8UL1TR000071NCATS NIH HHS UL1 TR000071NCI NIH HHS 3R01CA97959NCI NIH HHS R01 CA097959NCRR NIH HHS UL1 RR029876NHLBI NIH HHS 1P01 HL107152-01NHLBI NIH HHS P01 HL107152
6 · The paper itself

Abstract

Some extracellular proteins are initially secreted in reduced forms via a non-canonical pathway bypassing the endoplasmic reticulum and become oxidized in the extracellular space. One such protein is HMGB1 (high-mobility group box 1). Extracellular HMGB1 has different redox states that play distinct roles in inflammation. Using a unique NMR-based approach, we have investigated the kinetics of HMGB1 oxidation and the half-lives of all-thiol and disulfide HMGB1 species in serum, saliva, and cell culture medium. In this approach, salt-free lyophilized (15)N-labeled all-thiol HMGB1 was dissolved in actual extracellular fluids, and the oxidation and clearance kinetics were monitored in situ by recording a series of heteronuclear (1)H-(15)N correlation spectra. We found that the half-life depends significantly on the extracellular environment. For example, the half-life of all-thiol HMGB1 ranged from ~17 min (in human serum and saliva) to 3 h (in prostate cancer cell culture medium). Furthermore, the binding of ligands (glycyrrhizin and heparin) to HMGB1 significantly modulated the oxidation kinetics. Thus, the balance between the roles of all-thiol and disulfide HMGB1 proteins depends significantly on the extracellular environment and can also be artificially modulated by ligands. This is important because extracellular HMGB1 has been suggested as a therapeutic target for inflammatory diseases and cancer. Our work demonstrates that the in situ protein NMR approach is powerful for investigating the behavior of proteins in actual extracellular fluids containing an enormous number of different molecules.

Indexed as

AdultAgedCell Line, TumorHalf-LifeHMGB1 ProteinHumansKineticsMaleNuclear Magnetic Resonance, BiomolecularOxidation-ReductionSalivaHMGB1 Protein

Identifiers

PMID23447529
PMCPMC3636853
OpenAlexW2041441588

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.