Evidence map›Paper›PMID 30846619›Full record

ArticleThe Journal of pharmacology and experimental therapeutics2019

Mitochondrial Complex I Inhibition by Metformin Limits Reperfusion Injury.

Ahmed A Mohsin, Qun Chen, Nanhu Quan, Thomas Rousselle, Michael W Maceyka, Arun Samidurai, Jeremy Thompson, Ying Hu, Ji Li, Edward J Lesnefsky

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of pharmacology and experimental therapeutics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.

0numbers the graph read from it
0cells of the map it votes in
49citing papers in PubMed
8.8field-weighted citation impact, top 2% 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

49 citing papers in PubMed, 86 citations in OpenAlex.

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  5. Targeting mitochondria to protect the heart: a matter of balance?Clinical science (London, England : 1979) · 2025
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  13. The protective role of RACK1 in hepatic ischemia‒reperfusion injury-induced ferroptosis.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2024
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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

10 authors at 3 institutions in 1 country.

Ahmed A MohsinDepartment of Biochemistry and Molecular Biology (A.A.M., M.W.M., E.J.L.) and Pauley Heart Center, Division of Cardiology, Department of Internal Medicine (Q.C., A.S., J.T., Y.H., E.J.L.), Virginia Commonwealth University, Richmond, Virginia; Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi (N.Q., T.R., J.L.); and Cardiology Section Medical Service, McGuire Veterans Affairs Medical Center, Richmond, Virginia (E.J.L.).
Qun ChenDepartment of Biochemistry and Molecular Biology (A.A.M., M.W.M., E.J.L.) and Pauley Heart Center, Division of Cardiology, Department of Internal Medicine (Q.C., A.S., J.T., Y.H., E.J.L.), Virginia Commonwealth University, Richmond, Virginia; Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi (N.Q., T.R., J.L.); and Cardiology Section Medical Service, McGuire Veterans Affairs Medical Center, Richmond, Virginia (E.J.L.).
Nanhu QuanDepartment of Biochemistry and Molecular Biology (A.A.M., M.W.M., E.J.L.) and Pauley Heart Center, Division of Cardiology, Department of Internal Medicine (Q.C., A.S., J.T., Y.H., E.J.L.), Virginia Commonwealth University, Richmond, Virginia; Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi (N.Q., T.R., J.L.); and Cardiology Section Medical Service, McGuire Veterans Affairs Medical Center, Richmond, Virginia (E.J.L.).
Thomas RousselleDepartment of Biochemistry and Molecular Biology (A.A.M., M.W.M., E.J.L.) and Pauley Heart Center, Division of Cardiology, Department of Internal Medicine (Q.C., A.S., J.T., Y.H., E.J.L.), Virginia Commonwealth University, Richmond, Virginia; Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi (N.Q., T.R., J.L.); and Cardiology Section Medical Service, McGuire Veterans Affairs Medical Center, Richmond, Virginia (E.J.L.).
Michael W MaceykaDepartment of Biochemistry and Molecular Biology (A.A.M., M.W.M., E.J.L.) and Pauley Heart Center, Division of Cardiology, Department of Internal Medicine (Q.C., A.S., J.T., Y.H., E.J.L.), Virginia Commonwealth University, Richmond, Virginia; Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi (N.Q., T.R., J.L.); and Cardiology Section Medical Service, McGuire Veterans Affairs Medical Center, Richmond, Virginia (E.J.L.).
Arun SamiduraiDepartment of Biochemistry and Molecular Biology (A.A.M., M.W.M., E.J.L.) and Pauley Heart Center, Division of Cardiology, Department of Internal Medicine (Q.C., A.S., J.T., Y.H., E.J.L.), Virginia Commonwealth University, Richmond, Virginia; Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi (N.Q., T.R., J.L.); and Cardiology Section Medical Service, McGuire Veterans Affairs Medical Center, Richmond, Virginia (E.J.L.).
Jeremy ThompsonDepartment of Biochemistry and Molecular Biology (A.A.M., M.W.M., E.J.L.) and Pauley Heart Center, Division of Cardiology, Department of Internal Medicine (Q.C., A.S., J.T., Y.H., E.J.L.), Virginia Commonwealth University, Richmond, Virginia; Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi (N.Q., T.R., J.L.); and Cardiology Section Medical Service, McGuire Veterans Affairs Medical Center, Richmond, Virginia (E.J.L.).
Ying HuDepartment of Biochemistry and Molecular Biology (A.A.M., M.W.M., E.J.L.) and Pauley Heart Center, Division of Cardiology, Department of Internal Medicine (Q.C., A.S., J.T., Y.H., E.J.L.), Virginia Commonwealth University, Richmond, Virginia; Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi (N.Q., T.R., J.L.); and Cardiology Section Medical Service, McGuire Veterans Affairs Medical Center, Richmond, Virginia (E.J.L.).
Ji LiDepartment of Biochemistry and Molecular Biology (A.A.M., M.W.M., E.J.L.) and Pauley Heart Center, Division of Cardiology, Department of Internal Medicine (Q.C., A.S., J.T., Y.H., E.J.L.), Virginia Commonwealth University, Richmond, Virginia; Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi (N.Q., T.R., J.L.); and Cardiology Section Medical Service, McGuire Veterans Affairs Medical Center, Richmond, Virginia (E.J.L.).
Edward J LesnefskyDepartment of Biochemistry and Molecular Biology (A.A.M., M.W.M., E.J.L.) and Pauley Heart Center, Division of Cardiology, Department of Internal Medicine (Q.C., A.S., J.T., Y.H., E.J.L.), Virginia Commonwealth University, Richmond, Virginia; Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi (N.Q., T.R., J.L.); and Cardiology Section Medical Service, McGuire Veterans Affairs Medical Center, Richmond, Virginia (E.J.L.) edward.lesnefsky@va.gov.
Virginia Commonwealth University · USJackson Memorial Hospital · USUniversity of Mississippi Medical Center · US

Funding

AMPK-SIRT1 Signaling in the Adaptive Metabolic ResponseR01AG049835 · NIA · UNIVERSITY OF SOUTH FLORIDA · PI LI, JI N, · 2015 to 2019
$1.6M
Activated Protein C and Cardiac Inflammatory ResponseR01GM124108 · NIGMS · UNIVERSITY OF SOUTH FLORIDA · PI LI, JI N, · 2018 to 2021
$1.4M
activation of mitochondrial calpain augments cardiac injury in aged heartsR21AG054975 · NIA · VIRGINIA COMMONWEALTH UNIVERSITY · PI CHEN, QUN · 2017 to 2018
$433k
Reduction of cardiac injury by targeting damaged mitochondria during reperfusionI01BX001355 · VA · VA VETERANS ADMINISTRATION HOSPITAL · PI LESNEFSKY, EDWARD J · 2012 to 2025
–
BLRD VA I01 BX001355NIA NIH HHS R01 AG049835NIA NIH HHS R21 AG054975NIGMS NIH HHS R01 GM124108
6 · The paper itself

Abstract

Transient, reversible blockade of complex I during early reperfusion after ischemia limits cardiac injury. We studied the cardioprotection of high dose of metformin in cultured cells and mouse hearts via the novel mechanism of acute downregulation of complex I. The effect of high dose of metformin on complex I activity was studied in isolated heart mitochondria and cultured H9c2 cells. Protection with metformin was evaluated in H9c2 cells at reoxygenation and at early reperfusion in isolated perfused mouse hearts and in vivo regional ischemia reperfusion. Acute, high-dose metformin treatment inhibited complex I in ischemia-damaged mitochondria and in H9c2 cells following hypoxia. Accompanying the complex I modulation, high-dose metformin at reoxygenation decreased death in H9c2 cells. Acute treatment with high-dose metformin at the end of ischemia reduced infarct size following ischemia reperfusion in vitro and in vivo, including in the AMP kinase-dead mouse. Metformin treatment during early reperfusion improved mitochondrial calcium retention capacity, indicating decreased permeability transition pore (MPTP) opening. Acute, high-dose metformin therapy decreased cardiac injury through inhibition of complex I accompanied by attenuation of MPTP opening. Moreover, in contrast to chronic metformin treatment, protection by acute, high-dose metformin is independent of AMP-activated protein kinase activation. Thus, a single, high-dose metformin treatment at reperfusion reduces cardiac injury via modulation of complex I.

Indexed as

AMP-Activated Protein KinasesAnimalsCell LineCytoprotectionDose-Response Relationship, DrugElectron Transport Complex IEnzyme ActivationEnzyme InhibitorsMaleMetforminMiceMice, Inbred C57BLMitochondrial Membrane Transport ProteinsMitochondrial Permeability Transition PoreMyocardial Reperfusion InjuryProtein ConformationAMP-Activated Protein KinasesElectron Transport Complex IEnzyme InhibitorsMetforminMitochondrial Membrane Transport ProteinsMitochondrial Permeability Transition Pore

Identifiers

PMID30846619
PMCPMC6474909
OpenAlexW2922422823

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.