Evidence map›Paper›PMID 29419407›Full record

ArticleArteriosclerosis, thrombosis, and vascular biology2018

Hyperoxia Causes Mitochondrial Fragmentation in Pulmonary Endothelial Cells by Increasing Expression of Pro-Fission Proteins.

Cui Ma, Andreas M Beyer, Matthew Durand, Anne V Clough, Daling Zhu, Laura Norwood Toro, Maia Terashvili, Johnathan D Ebben, R Blake Hill, Said H Audi and 2 more

Open access · bronzeAbstract read
In one paragraph

Article in Arteriosclerosis, thrombosis, and vascular biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.

0numbers the graph read from it
0cells of the map it votes in
46citing papers in PubMed
3.0field-weighted citation impact, top 8% 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

46 citing papers in PubMed, 71 citations in OpenAlex.

  1. Article
  2. Hyperoxia and iron homeostasis in developing human airway smooth muscle.American journal of physiology. Lung cellular and molecular physiology · 2026
    Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Article
  8. Review
  9. Article
  10. Article
  11. Article
  12. [Role of reactive oxygen species/silent information regulator 1 in hyperoxia-induced bronchial epithelial cell injury].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2024
    Article
  13. Article
  14. Review
  15. Review
  16. Review
  17. Article
  18. Article
  19. 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

12 authors at 3 institutions in 2 countries.

Cui MaFrom the College of Medical Laboratory Science and Technology, Harbin Medical University, Daqing, China (C.M., D.Z., M.M., E.R.J.); Department of Medicine (C.M., A.M.B., A.C., L.N., J.E., M.M., E.R.J.), Department of Physical Medicine and Rehabilitation (M.D.), Department of Physiology (A.M.B., M.M., E.R.J.), Department of Biochemistry (B.H.), Department of Radiation Oncology (M.M.), Department of Biophysics (N.H.), and Cardiovascular Center (M.T., C.M., A.B., M.D., M.M., E.R.J.), Medical College of Wisconsin, Milwaukee; Research Service, Zablocki Veterans Affairs Medical Center, Milwaukee (A.C., S.H.A., M.M., E.R.J.); Department of Biomedical Engineering, Marquette University, Milwaukee (S.H.A.); and Department of Mathematics, Statistics and Computer Science, Marquette University, Milwaukee (A.C.).
Andreas M BeyerFrom the College of Medical Laboratory Science and Technology, Harbin Medical University, Daqing, China (C.M., D.Z., M.M., E.R.J.); Department of Medicine (C.M., A.M.B., A.C., L.N., J.E., M.M., E.R.J.), Department of Physical Medicine and Rehabilitation (M.D.), Department of Physiology (A.M.B., M.M., E.R.J.), Department of Biochemistry (B.H.), Department of Radiation Oncology (M.M.), Department of Biophysics (N.H.), and Cardiovascular Center (M.T., C.M., A.B., M.D., M.M., E.R.J.), Medical College of Wisconsin, Milwaukee; Research Service, Zablocki Veterans Affairs Medical Center, Milwaukee (A.C., S.H.A., M.M., E.R.J.); Department of Biomedical Engineering, Marquette University, Milwaukee (S.H.A.); and Department of Mathematics, Statistics and Computer Science, Marquette University, Milwaukee (A.C.).
Matthew DurandFrom the College of Medical Laboratory Science and Technology, Harbin Medical University, Daqing, China (C.M., D.Z., M.M., E.R.J.); Department of Medicine (C.M., A.M.B., A.C., L.N., J.E., M.M., E.R.J.), Department of Physical Medicine and Rehabilitation (M.D.), Department of Physiology (A.M.B., M.M., E.R.J.), Department of Biochemistry (B.H.), Department of Radiation Oncology (M.M.), Department of Biophysics (N.H.), and Cardiovascular Center (M.T., C.M., A.B., M.D., M.M., E.R.J.), Medical College of Wisconsin, Milwaukee; Research Service, Zablocki Veterans Affairs Medical Center, Milwaukee (A.C., S.H.A., M.M., E.R.J.); Department of Biomedical Engineering, Marquette University, Milwaukee (S.H.A.); and Department of Mathematics, Statistics and Computer Science, Marquette University, Milwaukee (A.C.).
Anne V CloughFrom the College of Medical Laboratory Science and Technology, Harbin Medical University, Daqing, China (C.M., D.Z., M.M., E.R.J.); Department of Medicine (C.M., A.M.B., A.C., L.N., J.E., M.M., E.R.J.), Department of Physical Medicine and Rehabilitation (M.D.), Department of Physiology (A.M.B., M.M., E.R.J.), Department of Biochemistry (B.H.), Department of Radiation Oncology (M.M.), Department of Biophysics (N.H.), and Cardiovascular Center (M.T., C.M., A.B., M.D., M.M., E.R.J.), Medical College of Wisconsin, Milwaukee; Research Service, Zablocki Veterans Affairs Medical Center, Milwaukee (A.C., S.H.A., M.M., E.R.J.); Department of Biomedical Engineering, Marquette University, Milwaukee (S.H.A.); and Department of Mathematics, Statistics and Computer Science, Marquette University, Milwaukee (A.C.).
Daling ZhuFrom the College of Medical Laboratory Science and Technology, Harbin Medical University, Daqing, China (C.M., D.Z., M.M., E.R.J.); Department of Medicine (C.M., A.M.B., A.C., L.N., J.E., M.M., E.R.J.), Department of Physical Medicine and Rehabilitation (M.D.), Department of Physiology (A.M.B., M.M., E.R.J.), Department of Biochemistry (B.H.), Department of Radiation Oncology (M.M.), Department of Biophysics (N.H.), and Cardiovascular Center (M.T., C.M., A.B., M.D., M.M., E.R.J.), Medical College of Wisconsin, Milwaukee; Research Service, Zablocki Veterans Affairs Medical Center, Milwaukee (A.C., S.H.A., M.M., E.R.J.); Department of Biomedical Engineering, Marquette University, Milwaukee (S.H.A.); and Department of Mathematics, Statistics and Computer Science, Marquette University, Milwaukee (A.C.).
Laura Norwood ToroFrom the College of Medical Laboratory Science and Technology, Harbin Medical University, Daqing, China (C.M., D.Z., M.M., E.R.J.); Department of Medicine (C.M., A.M.B., A.C., L.N., J.E., M.M., E.R.J.), Department of Physical Medicine and Rehabilitation (M.D.), Department of Physiology (A.M.B., M.M., E.R.J.), Department of Biochemistry (B.H.), Department of Radiation Oncology (M.M.), Department of Biophysics (N.H.), and Cardiovascular Center (M.T., C.M., A.B., M.D., M.M., E.R.J.), Medical College of Wisconsin, Milwaukee; Research Service, Zablocki Veterans Affairs Medical Center, Milwaukee (A.C., S.H.A., M.M., E.R.J.); Department of Biomedical Engineering, Marquette University, Milwaukee (S.H.A.); and Department of Mathematics, Statistics and Computer Science, Marquette University, Milwaukee (A.C.).
Maia TerashviliFrom the College of Medical Laboratory Science and Technology, Harbin Medical University, Daqing, China (C.M., D.Z., M.M., E.R.J.); Department of Medicine (C.M., A.M.B., A.C., L.N., J.E., M.M., E.R.J.), Department of Physical Medicine and Rehabilitation (M.D.), Department of Physiology (A.M.B., M.M., E.R.J.), Department of Biochemistry (B.H.), Department of Radiation Oncology (M.M.), Department of Biophysics (N.H.), and Cardiovascular Center (M.T., C.M., A.B., M.D., M.M., E.R.J.), Medical College of Wisconsin, Milwaukee; Research Service, Zablocki Veterans Affairs Medical Center, Milwaukee (A.C., S.H.A., M.M., E.R.J.); Department of Biomedical Engineering, Marquette University, Milwaukee (S.H.A.); and Department of Mathematics, Statistics and Computer Science, Marquette University, Milwaukee (A.C.).
Johnathan D EbbenFrom the College of Medical Laboratory Science and Technology, Harbin Medical University, Daqing, China (C.M., D.Z., M.M., E.R.J.); Department of Medicine (C.M., A.M.B., A.C., L.N., J.E., M.M., E.R.J.), Department of Physical Medicine and Rehabilitation (M.D.), Department of Physiology (A.M.B., M.M., E.R.J.), Department of Biochemistry (B.H.), Department of Radiation Oncology (M.M.), Department of Biophysics (N.H.), and Cardiovascular Center (M.T., C.M., A.B., M.D., M.M., E.R.J.), Medical College of Wisconsin, Milwaukee; Research Service, Zablocki Veterans Affairs Medical Center, Milwaukee (A.C., S.H.A., M.M., E.R.J.); Department of Biomedical Engineering, Marquette University, Milwaukee (S.H.A.); and Department of Mathematics, Statistics and Computer Science, Marquette University, Milwaukee (A.C.).
R Blake HillFrom the College of Medical Laboratory Science and Technology, Harbin Medical University, Daqing, China (C.M., D.Z., M.M., E.R.J.); Department of Medicine (C.M., A.M.B., A.C., L.N., J.E., M.M., E.R.J.), Department of Physical Medicine and Rehabilitation (M.D.), Department of Physiology (A.M.B., M.M., E.R.J.), Department of Biochemistry (B.H.), Department of Radiation Oncology (M.M.), Department of Biophysics (N.H.), and Cardiovascular Center (M.T., C.M., A.B., M.D., M.M., E.R.J.), Medical College of Wisconsin, Milwaukee; Research Service, Zablocki Veterans Affairs Medical Center, Milwaukee (A.C., S.H.A., M.M., E.R.J.); Department of Biomedical Engineering, Marquette University, Milwaukee (S.H.A.); and Department of Mathematics, Statistics and Computer Science, Marquette University, Milwaukee (A.C.).
Said H AudiFrom the College of Medical Laboratory Science and Technology, Harbin Medical University, Daqing, China (C.M., D.Z., M.M., E.R.J.); Department of Medicine (C.M., A.M.B., A.C., L.N., J.E., M.M., E.R.J.), Department of Physical Medicine and Rehabilitation (M.D.), Department of Physiology (A.M.B., M.M., E.R.J.), Department of Biochemistry (B.H.), Department of Radiation Oncology (M.M.), Department of Biophysics (N.H.), and Cardiovascular Center (M.T., C.M., A.B., M.D., M.M., E.R.J.), Medical College of Wisconsin, Milwaukee; Research Service, Zablocki Veterans Affairs Medical Center, Milwaukee (A.C., S.H.A., M.M., E.R.J.); Department of Biomedical Engineering, Marquette University, Milwaukee (S.H.A.); and Department of Mathematics, Statistics and Computer Science, Marquette University, Milwaukee (A.C.).
Meetha MedhoraFrom the College of Medical Laboratory Science and Technology, Harbin Medical University, Daqing, China (C.M., D.Z., M.M., E.R.J.); Department of Medicine (C.M., A.M.B., A.C., L.N., J.E., M.M., E.R.J.), Department of Physical Medicine and Rehabilitation (M.D.), Department of Physiology (A.M.B., M.M., E.R.J.), Department of Biochemistry (B.H.), Department of Radiation Oncology (M.M.), Department of Biophysics (N.H.), and Cardiovascular Center (M.T., C.M., A.B., M.D., M.M., E.R.J.), Medical College of Wisconsin, Milwaukee; Research Service, Zablocki Veterans Affairs Medical Center, Milwaukee (A.C., S.H.A., M.M., E.R.J.); Department of Biomedical Engineering, Marquette University, Milwaukee (S.H.A.); and Department of Mathematics, Statistics and Computer Science, Marquette University, Milwaukee (A.C.).
Elizabeth R JacobsFrom the College of Medical Laboratory Science and Technology, Harbin Medical University, Daqing, China (C.M., D.Z., M.M., E.R.J.); Department of Medicine (C.M., A.M.B., A.C., L.N., J.E., M.M., E.R.J.), Department of Physical Medicine and Rehabilitation (M.D.), Department of Physiology (A.M.B., M.M., E.R.J.), Department of Biochemistry (B.H.), Department of Radiation Oncology (M.M.), Department of Biophysics (N.H.), and Cardiovascular Center (M.T., C.M., A.B., M.D., M.M., E.R.J.), Medical College of Wisconsin, Milwaukee; Research Service, Zablocki Veterans Affairs Medical Center, Milwaukee (A.C., S.H.A., M.M., E.R.J.); Department of Biomedical Engineering, Marquette University, Milwaukee (S.H.A.); and Department of Mathematics, Statistics and Computer Science, Marquette University, Milwaukee (A.C.). ejacobs@mcw.edu.
Milwaukee VA Medical Center · USMarquette University · USHarbin Medical University · CN

Funding

Clincal and Translational Science AwardUL1TR000055 · NCATS · MEDICAL COLLEGE OF WISCONSIN · PI SHAKER, REZA NONE · 2012 to 2015
$11.3M
Structural Biology of Mitochondrial FissionR01GM067180 · NIGMS · MEDICAL COLLEGE OF WISCONSIN · PI HILL, R BLAKE · 2004 to 2022
$6.0M
Development of lisinopril for post-exposure mitigation of late effects from a radU01AI107305 · NIAID · MEDICAL COLLEGE OF WISCONSIN · PI MEDHORA, MEETHA M · 2013 to 2017
$3.0M
Mechanism of radiation induced endovascular injury and mitigation via the Notch-Dll4 pathwayU01AI133594 · NIAID · MEDICAL COLLEGE OF WISCONSIN · PI HIMBURG, HEATHER A · 2018 to 2022
$3.0M
Endothelial function in human diabetes: role of mitochondrial fission proteinsR01HL128240 · NHLBI · MEDICAL COLLEGE OF WISCONSIN · PI WIDLANSKY, MICHAEL E · 2016 to 2020
$2.9M
Pivotal Role of Mitochondrial Telomerase in Regulation of Vascular Tone and Redox HomeostasisR01HL133029 · NHLBI · MEDICAL COLLEGE OF WISCONSIN · PI BEYER, ANDREAS M · 2017 to 2021
$2.2M
Innovative Biomarkers to Predict Radiation Lung InjuryR01AI101898 · NIAID · MEDICAL COLLEGE OF WISCONSIN · PI MEDHORA, MEETHA M · 2012 to 2016
$1.9M
SPECT Imaging and Computational Modeling for Assessment of Acute Lung InjuryR15HL129209 · NHLBI · MARQUETTE UNIVERSITY · PI SAID H AUDI · 2015 to 2026
$1.8M
Novel imaging to identify lung mitochondrial injury and predict recoveryR01HL116530 · NHLBI · MEDICAL COLLEGE OF WISCONSIN · PI JACOBS, ELIZABETH R · 2013 to 2016
$1.1M
Differentiation of mitochondrial vs. nuclear function of telomeraseR21OD018306 · OD · MEDICAL COLLEGE OF WISCONSIN · PI BEYER, ANDREAS M · 2014 to 2015
$411k
Novel Diagnostics to Detect Lung InjuryI01BX001681 · VA · CLEMENT J. ZABLOCKI VA MEDICAL CENTER · PI JACOBS, ELIZABETH R · 2013 to 2016
–
BLRD VA I01 BX001681BLRD VA I01 BX003833NCATS NIH HHS UL1 TR000055NHLBI NIH HHS R01 HL116530NHLBI NIH HHS R01 HL128240NHLBI NIH HHS R01 HL133029NHLBI NIH HHS R15 HL129209NIAID NIH HHS R01 AI101898NIAID NIH HHS U01 AI107305NIAID NIH HHS U01 AI133594NIGMS NIH HHS R01 GM067180NIH HHS R21 OD018306
6 · The paper itself

Abstract

objectiveWe explored mechanisms that alter mitochondrial structure and function in pulmonary endothelial cells (PEC) function after hyperoxia. APPROACH AND

resultsMitochondrial structures of PECs exposed to hyperoxia or normoxia were visualized and mitochondrial fragmentation quantified. Expression of pro-fission or fusion proteins or autophagy-related proteins were assessed by Western blot. Mitochondrial oxidative state was determined using mito-roGFP. Tetramethylrhodamine methyl ester estimated mitochondrial polarization in treatment groups. The role of mitochondrially derived reactive oxygen species in mt-fragmentation was investigated with mito-TEMPOL and mitochondrial DNA (mtDNA) damage studied by using ENDO III (mt-tat-endonuclease III), a protein that repairs mDNA damage. Drp-1 (dynamin-related protein 1) was overexpressed or silenced to test the role of this protein in cell survival or transwell resistance. Hyperoxia increased fragmentation of PEC mitochondria in a time-dependent manner through 48 hours of exposure. Hyperoxic PECs exhibited increased phosphorylation of Drp-1 (serine 616), decreases in Mfn1 (mitofusion protein 1), but increases in OPA-1 (optic atrophy 1). Pro-autophagy proteins p62 (LC3 adapter-binding protein SQSTM1/p62), PINK-1 (PTEN-induced putative kinase 1), and LC3B (microtubule-associated protein 1A/1B-light chain 3) were increased. Returning cells to normoxia for 24 hours reversed the increased mt-fragmentation and changes in expression of pro-fission proteins. Hyperoxia-induced changes in mitochondrial structure or cell survival were mitigated by antioxidants mito-TEMPOL, Drp-1 silencing, or inhibition or protection by the mitochondrial endonuclease ENDO III. Hyperoxia induced oxidation and mitochondrial depolarization and impaired transwell resistance. Decrease in resistance was mitigated by mito-TEMPOL or ENDO III and reproduced by overexpression of Drp-1.

conclusionsBecause hyperoxia evoked mt-fragmentation, cell survival and transwell resistance are prevented by ENDO III and mito-TEMPOL and Drp-1 silencing, and these data link hyperoxia-induced mt-DNA damage, Drp-1 expression, mt-fragmentation, and PEC dysfunction.

Indexed as

AnimalsAntioxidantsDynaminsEndothelial CellsHyperoxiaMitochondriaMitochondrial DynamicsMitochondrial ProteinsOxidative StressOxygenPulmonary ArteryRatsReactive Oxygen SpeciesUp-RegulationAntioxidantsDnm1l protein, ratDynaminsMitochondrial ProteinsOxygenReactive Oxygen Speciescell survivalendothelial cellshyperoxiamitochondriareactive oxygen species

Identifiers

PMID29419407
PMCPMC5823793
OpenAlexW2785825884

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.