Evidence map›Paper›PMID 24755204›Full record

ArticleNitric oxide : biology and chemistry2014

AP39, a novel mitochondria-targeted hydrogen sulfide donor, stimulates cellular bioenergetics, exerts cytoprotective effects and protects against the loss of mitochondrial DNA integrity in oxidatively stressed endothelial cells in vitro.

Bartosz Szczesny, Katalin Módis, Kazunori Yanagi, Ciro Coletta, Sophie Le Trionnaire, Alexis Perry, Mark E Wood, Matthew Whiteman, Csaba Szabo

Abstract read
In one paragraph

Article in Nitric oxide : biology and chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 139 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
139citing papers in PubMed, 1 pooled it
15.5field-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

139 citing papers in PubMed, 1 synthesis or guideline pooled it, 285 citations in OpenAlex.

  1. The Protective Effect of Puerarin on Myocardial Infarction Reperfusion Injury (MIRI): A Meta-Analysis of Randomized Studies in Rat Models.Medical science monitor : international medical journal of experimental and clinical research · 2015
    Pooled it
  2. Review
  3. Review
  4. Review
  5. SQOR regulates HResearch square · 2026
    Article
  6. Article
  7. A Paradigm Shift of HCurrent issues in molecular biology · 2026
    Review
  8. Review
  9. Review
  10. Article
  11. Article
  12. Review
  13. Review
  14. Review
  15. Black gas, bright future: HNeurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025
    Review
  16. Intersection of HNeurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025
    Review
  17. Sulfide regulation and catabolism in health and disease.Signal transduction and targeted therapy · 2025
    Review
  18. The Dual Role of Exogenous Hydrogen Sulfide (HAntioxidants (Basel, Switzerland) · 2025
    Article
  19. Review
  20. Review

79 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

9 authors at 2 institutions in 2 countries.

Bartosz SzczesnyDepartment of Anesthesiology, University of Texas Medical Branch, Galveston, TX, USA.
Katalin MódisDepartment of Anesthesiology, University of Texas Medical Branch, Galveston, TX, USA.
Kazunori YanagiDepartment of Anesthesiology, University of Texas Medical Branch, Galveston, TX, USA.
Ciro ColettaDepartment of Anesthesiology, University of Texas Medical Branch, Galveston, TX, USA.
Sophie Le TrionnaireUniversity of Exeter Medical School, St. Luke's Campus, Exeter, England, United Kingdom.
Alexis PerryBiosciences, College of Life and Environmental Science, University of Exeter, England, United Kingdom.
Mark E WoodBiosciences, College of Life and Environmental Science, University of Exeter, England, United Kingdom.
Matthew WhitemanUniversity of Exeter Medical School, St. Luke's Campus, Exeter, England, United Kingdom. Electronic address: m.whiteman@exeter.ac.uk.
Csaba SzaboDepartment of Anesthesiology, University of Texas Medical Branch, Galveston, TX, USA. Electronic address: szabocsaba@aol.com.
The University of Texas Medical Branch at Galveston · USUniversity of Exeter · GB

Funding

Regulation of cellular bioenergetics by hydrogen sulfideR01GM107846 · NIGMS · UNIVERSITY OF TEXAS MED BR GALVESTON · PI SZABO, CSABA · 2014 to 2017
$1.2M
Medical Research CouncilNIGMS NIH HHS R01 GM107846NIGMS NIH HHS R01GM107846
6 · The paper itself

Abstract

The purpose of the current study was to investigate the effect of the recently synthesized mitochondrially-targeted H2S donor, AP39 [(10-oxo-10-(4-(3-thioxo-3H-1,2-dithiol-5yl)phenoxy)decyl) triphenylphosphonium bromide], on bioenergetics, viability, and mitochondrial DNA integrity in bEnd.3 murine microvascular endothelial cells in vitro, under normal conditions, and during oxidative stress. Intracellular H2S was assessed by the fluorescent dye 7-azido-4-methylcoumarin. For the measurement of bioenergetic function, the XF24 Extracellular Flux Analyzer was used. Cell viability was estimated by the combination of the MTT and LDH methods. Oxidative protein modifications were measured by the Oxyblot method. Reactive oxygen species production was monitored by the MitoSOX method. Mitochondrial and nuclear DNA integrity were assayed by the Long Amplicon PCR method. Oxidative stress was induced by addition of glucose oxidase. Addition of AP39 (30-300 nM) to bEnd.3 cells increased intracellular H2S levels, with a preferential response in the mitochondrial regions. AP39 exerted a concentration-dependent effect on mitochondrial activity, which consisted of a stimulation of mitochondrial electron transport and cellular bioenergetic function at lower concentrations (30-100 nM) and an inhibitory effect at the higher concentration of 300 nM. Under oxidative stress conditions induced by glucose oxidase, an increase in oxidative protein modification and an enhancement in MitoSOX oxidation was noted, coupled with an inhibition of cellular bioenergetic function and a reduction in cell viability. AP39 pretreatment attenuated these responses. Glucose oxidase induced a preferential damage to the mitochondrial DNA; AP39 (100 nM) pretreatment protected against it. In conclusion, the current paper documents antioxidant and cytoprotective effects of AP39 under oxidative stress conditions, including a protection against oxidative mitochondrial DNA damage.

Indexed as

AnimalsCell LineDNA, MitochondrialDNA RepairEndothelial CellsGlucose OxidaseHydrogen PeroxideHydrogen SulfideIntracellular SpaceMiceOrganophosphatesOrganophosphorus CompoundsOxidative StressProtective AgentsThionesAP39 compoundDNA, MitochondrialGlucose OxidaseHydrogen PeroxideHydrogen SulfideOrganophosphatesOrganophosphorus CompoundsProtective AgentsThionesBioenergeticsCytoprotectionDNA repairMitochondriaOxidative stress

Identifiers

PMID24755204
PMCPMC4225488
OpenAlexW2084982869

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.