Evidence map›Paper›PMID 26855417›Full record

ArticleFree radical biology & medicine2016

The circadian gene Rev-erbα improves cellular bioenergetics and provides preconditioning for protection against oxidative stress.

Shaon Sengupta, Guang Yang, John C O'Donnell, Maurice D Hinson, Shana E McCormack, Marni J Falk, Ping La, Michael B Robinson, Monica L Williams, Mekdes T Yohannes and 3 more

Open access · greenAbstract read
In one paragraph

Article in Free radical biology & medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
2.3field-weighted citation impact, top 13% 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

28 citing papers in PubMed, 49 citations in OpenAlex.

  1. Article
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  4. Review
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  8. Review
  9. Pharmacological Activation of Rev-erbCardiovascular therapeutics · 2023
    Article
  10. Review
  11. Article
  12. Review
  13. Article
  14. Exploring the Genetic Conception of Obesity via the Dual Role of FoxO.International journal of molecular sciences · 2021
    Review
  15. Review
  16. Article
  17. Article
  18. Article
  19. Keeping time in group 3 innate lymphoid cells.Nature reviews. Immunology · 2020
    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

13 authors at 2 institutions in 1 country.

Shaon SenguptaDivision of Neonatology, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; University of Pennsylvania, Philadelphia, PA 19104, USA.
Guang YangDivision of Neonatology, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
John C O'DonnellUniversity of Pennsylvania, Philadelphia, PA 19104, USA.
Maurice D HinsonDivision of Neonatology, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Shana E McCormackUniversity of Pennsylvania, Philadelphia, PA 19104, USA; Division of Endocrinology, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Marni J FalkUniversity of Pennsylvania, Philadelphia, PA 19104, USA; Division of Genetics and Metabolism, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Ping LaDivision of Neonatology, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Michael B RobinsonUniversity of Pennsylvania, Philadelphia, PA 19104, USA; Division of Developmental and Behavioral Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Monica L WilliamsDivision of Neonatology, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Mekdes T YohannesDivision of Neonatology, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Erzsebet PolyakDivision of Genetics and Metabolism, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Eiko Nakamaru-OgisoUniversity of Pennsylvania, Philadelphia, PA 19104, USA.
Phyllis A DenneryDivision of Neonatology, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; University of Pennsylvania, Philadelphia, PA 19104, USA.
Children's Hospital of Philadelphia · USUniversity of Pennsylvania · US

Funding

PREDOCTORAL TRAINING PROGRAM IN PHARMACOLOGYT32GM008076 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI BLENDY, JULIE A · 1985 to 2023
$10.8M
Pediatric Scholars ProgramK12HD043245 · NICHD · CHILDREN'S HOSP OF PHILADELPHIA · PI ST. GEME, JOSEPH W. · 2003 to 2022
$7.4M
The Intellectual and Developmental Disabilities Research Center at CHOP/PennU54HD086984 · NICHD · CHILDREN'S HOSP OF PHILADELPHIA · PI ROBERTS, TIMOTHY P · 2016 to 2020
$6.3M
Role of Heme Oxygenase in Neonatal Hyperoxic InjuryR01HL058752 · NHLBI · STANFORD UNIVERSITY · PI DENNERY, PHYLLIS A. · 1999 to 2013
$4.5M
Career Development Program in Pediatric Diabetes Research (K12) at CHOPK12DK094723 · NIDDK · CHILDREN'S HOSP OF PHILADELPHIA · PI WILLI, STEVEN M · 2011 to 2020
$3.6M
REGULATION OF EXTRACELLULAR EXCITOTOXINSR01NS029868 · NINDS · CHILDREN'S HOSP OF PHILADELPHIA · PI ROBINSON, MICHAEL BYRNE · 1993 to 2006
$1.8M
Regulation of Extracellular ExcitotoxinsR01HD060132 · NICHD · CHILDREN'S HOSP OF PHILADELPHIA · PI ROBINSON, MICHAEL BYRNE · 2008 to 2012
$1.7M
Astroglial Glutamate Transporters, Energetics, and MitochondriaR01NS077773 · NINDS · CHILDREN'S HOSP OF PHILADELPHIA · PI ROBINSON, MICHAEL BYRNE · 2012 to 2015
$1.4M
Training Program in Genome-Environment Interactions in Neonatal DiseaseT32HD060556 · NICHD · CHILDREN'S HOSP OF PHILADELPHIA · PI WORTHEN, GEORGE SCOTT · 2010 to 2014
$922k
Regulation of the Lung Circadian Clock by Heme Oxygenase-1R21HL111907 · NHLBI · CHILDREN'S HOSP OF PHILADELPHIA · PI DENNERY, PHYLLIS A. · 2013 to 2014
$520k
Translational investigation of abnormal fat metabolism in mitochondrial diseaseK23DK102659 · NIDDK · CHILDREN'S HOSP OF PHILADELPHIA · PI MCCORMACK, SHANA ERIN · 2015 to 2017
$515k
Mitochondrial dynamics in astrocytic processes after transient ischemiaF31NS086255 · NINDS · UNIVERSITY OF PENNSYLVANIA · PI O'DONNELL, JOHN CHARLES · 2014 to 2016
$88k
NHLBI NIH HHS R01 HL058752NHLBI NIH HHS R01HL058752NHLBI NIH HHS R21 HL111907NHLBI NIH HHS R21-HL111907NICHD NIH HHS K12 HD043245NICHD NIH HHS R01 HD060132NICHD NIH HHS T32 HD060556NICHD NIH HHS T32HD60556-4NICHD NIH HHS U54 HD086984NIDDK NIH HHS K12 DK094723NIDDK NIH HHS K23 DK102659NIGMS NIH HHS T32 GM008076NIGMS NIH HHS T32GM008076NINDS NIH HHS F31 NS086255NINDS NIH HHS R01 NS029868NINDS NIH HHS R01 NS077773NINDS NIH HHS R01NS077773
6 · The paper itself

Abstract

Diurnal oscillations in the expression of antioxidant genes imply that protection against oxidative stress is circadian-gated. We hypothesized that stabilization of the core circadian gene Rev-erbα (Nr1d1) improves cellular bioenergetics and protects against nutrient deprivation and oxidative stress. Compared to WT, mouse lung fibroblasts (MLG) stably transfected with a degradation resistant Rev-erbα (Ser(55/59) to Asp; hence referred to as SD) had 40% higher protein content, 1.5-fold higher mitochondrial area (confocal microscopy), doubled oxidative phosphorylation by high-resolution respirometry (Oroboros) and were resistant to glucose deprivation for 24h. This resulted from a 4-fold reduction in mitophagy (L3CB co-localized with MitoTracker Red) versus WT. Although PGC1α protein expression was comparable between SD and WT MLG cells, the role of mitochondrial biogenesis in explaining increased mitochondrial mass in SD cells was less clear. Embryonic fibroblasts (MEF) from C57Bl/6-SD transgenic mice, had a 9-fold induction of FoxO1 mRNA and increased mRNA of downstream antioxidant targets heme oxygenase-1 (HO-1), Mn superoxide dismutase and catalase (1.5, 2 fold and 2 fold respectively) versus WT. This allowed the SD cells to survive 1h incubation with 500 µM H2O2 as well as 24h of exposure to 95% O2 and remain attached whereas most WT cells did not. These observations establish a mechanistic link between the metabolic functions of Rev-erbα with mitochondrial homeostasis and protection against oxidative stress.

Indexed as

AnimalsAntioxidantsCatalaseEnergy MetabolismFibroblastsHeme Oxygenase-1Hydrogen PeroxideMiceMice, TransgenicMitochondriaNuclear Receptor Subfamily 1, Group D, Member 1Oxidative StressPeroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alphaSuperoxide DismutaseAntioxidantsCatalaseHeme Oxygenase-1Hydrogen PeroxideNr1d1 protein, mouseNuclear Receptor Subfamily 1, Group D, Member 1Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alphaSuperoxide DismutaseBioenergeticsCircadianEnergy metabolismMitochondriaNR1D1Oxidative stressPeroxisome proliferator‐activated receptor gamma coactivator 1‐alpha (PGC‐1α)(PPARGC1A)Preconditioning

Identifiers

PMID26855417
PMCPMC4905744
OpenAlexW2322120913

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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.