Evidence map›Paper›PMID 23912160›Full record

ArticleFree radical biology & medicine2013

Depleted energy charge and increased pulmonary endothelial permeability induced by mitochondrial complex I inhibition are mitigated by coenzyme Q1 in the isolated perfused rat lung.

Robert D Bongard, Ke Yan, Raymond G Hoffmann, Said H Audi, Xiao Zhang, Brian J Lindemer, Mary I Townsley, Marilyn P Merker

Open access · greenAbstract read
In one paragraph

Article in Free radical biology & medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
1.2field-weighted citation impact, top 22% 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

19 citing papers in PubMed, 24 citations in OpenAlex.

  1. Article
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  6. In vivo molecular imaging stratifies rats with different susceptibilities to hyperoxic acute lung injury.American journal of physiology. Lung cellular and molecular physiology · 2022
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  16. Biomarkers for Radiation Pneumonitis Using Noninvasive Molecular Imaging.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2016
    Article
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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

8 authors at 2 institutions in 1 country.

Robert D BongardDepartment of Pulmonary Medicine, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Ke YanDepartment of Biostatistics, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Raymond G HoffmannDepartment of Biostatistics, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Said H AudiDepartment of Biomedical Engineering, Marquette University, Milwaukee, WI 53201, USA.
Xiao ZhangDepartment of Biomedical Engineering, Marquette University, Milwaukee, WI 53201, USA.
Brian J LindemerDepartment of Anesthesiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Mary I TownsleyDepartment of Physiology and Department of Medicine, University of South Alabama, Mobile, AL 36688, USA.
Marilyn P MerkerDepartment of Anesthesiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA; Department of Pharmacology/Toxicology, Medical College of Wisconsin, Milwaukee, WI 53226, USA; Zablocki Veterans Administration Medical Center, Milwaukee, WI 53295, USA. Electronic address: mmerker@mcw.edu.
Medical College of Wisconsin · USMarquette University · US

Funding

Pilot Project ProgramP30ES004184 · NIEHS · UNIVERSITY OF WISCONSIN MILWAUKEE · PI PETERING, DAVID HAROLD · 1987 to 2015
$11.8M
Clincal and Translational Science AwardUL1TR000055 · NCATS · MEDICAL COLLEGE OF WISCONSIN · PI SHAKER, REZA NONE · 2012 to 2015
$11.3M
NCATS NIH HHS NIH8UL1TR000055NCATS NIH HHS UL1 TR000055NIEHS NIH HHS NIEHS2P30ES004184-22A1NIEHS NIH HHS P30 ES004184
6 · The paper itself

Abstract

Mitochondrial dysfunction is associated with various forms of lung injury and disease that also involve alterations in pulmonary endothelial permeability, but the relationship, if any, between the two is not well understood. This question was addressed by perfusing isolated intact rat lung with a buffered physiological saline solution in the absence or presence of the mitochondrial complex I inhibitor rotenone (20 μM). Compared to control, rotenone depressed whole lung tissue ATP from 5.66 ± 0.46 (SEM) to 2.34 ± 0.15 µmol · g(-1) dry lung, with concomitant increases in the ADP:ATP and AMP:ATP ratios. Rotenone also increased lung perfusate lactate (from 12.36 ± 1.64 to 38.62 ± 3.14 µmol · 15 min(-1) perfusion · g(-1) dry lung) and the lactate:pyruvate ratio, but had no detectable impact on lung tissue GSH:GSSG redox status. The amphipathic quinone coenzyme Q1 (CoQ1; 50 μM) mitigated the impact of rotenone on the adenine nucleotide balance, wherein mitigation was blocked by NAD(P)H-quinone oxidoreductase 1 or mitochondrial complex III inhibitors. In separate studies, rotenone increased the pulmonary vascular endothelial filtration coefficient (Kf) from 0.043 ± 0.010 to 0.156 ± 0.037 ml · min(-1) · cm H2O(-1) · g(-1) dry lung, and CoQ1 protected against the effect of rotenone on Kf. A second complex I inhibitor, piericidin A, qualitatively reproduced the impact of rotenone on Kf and the lactate:pyruvate ratio. Taken together, the observations imply that pulmonary endothelial barrier integrity depends on mitochondrial bioenergetics as reflected in lung tissue ATP levels and that compensatory activation of whole lung glycolysis cannot protect against pulmonary endothelial hyperpermeability in response to mitochondrial blockade. The study further suggests that low-molecular-weight amphipathic quinones may have therapeutic utility in protecting lung barrier function in mitochondrial insufficiency.

Indexed as

Adenosine TriphosphateAnimalsAnti-Bacterial AgentsBlood-Air BarrierCapillary PermeabilityElectron Transport Complex IElectron Transport Complex IIIEndothelium, VascularEnergy MetabolismGlycolysisLactic AcidLungLung InjuryMaleMitochondriaNAD(P)H Dehydrogenase (Quinone)Adenosine TriphosphateAnti-Bacterial AgentsElectron Transport Complex IElectron Transport Complex IIILactic AcidNAD(P)H Dehydrogenase (Quinone)NQO1 protein, ratpiericidin APyridinesPyruvic AcidRotenoneUbiquinoneUbiquinone Q1Uncoupling AgentsFree radicalsMitochondrial electron transport complex IPerfused lungPulmonary endothelial filtration coefficientPulmonary endothelial permeabilityPulmonary endotheliumQuinone

Identifiers

PMID23912160
PMCPMC3924785
OpenAlexW1974475788

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.