Evidence map›Paper›PMID 23536361›Full record

ArticleCirculation2013

Type 5 adenylyl cyclase increases oxidative stress by transcriptional regulation of manganese superoxide dismutase via the SIRT1/FoxO3a pathway.

Lo Lai, Lin Yan, Shumin Gao, Che-Lin Hu, Hui Ge, Amy Davidow, Misun Park, Claudio Bravo, Kousaku Iwatsubo, Yoshihiro Ishikawa and 4 more

Open access · bronzeAbstract read
In one paragraph

Article in Circulation, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.

0numbers the graph read from it
0cells of the map it votes in
51citing papers in PubMed
7.5field-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

51 citing papers in PubMed, 100 citations in OpenAlex.

  1. Annexin A4 Deficient Ventricular Myocytes Display Advanced Hypertrophy and Electrical Remodeling With Chronic β-Adrenoceptor Stimulation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026
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  10. Antioxidant Activity in Extracts fromMolecules (Basel, Switzerland) · 2023
    Review
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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

14 authors at 1 institution in 1 country.

Lo LaiDepartment of Cell Biology & Molecular Medicine, University of Medicine & Dentistry of New Jersey, New Jersey Medical School, 185 South Orange Avenue, Newark, NJ 07103, USA. vatnerdo@umdnj.edu
Lin Yan
Shumin Gao
Che-Lin Hu
Hui Ge
Amy Davidow
Misun Park
Claudio Bravo
Kousaku Iwatsubo
Yoshihiro Ishikawa
Johan Auwerx
David A Sinclair
Stephen F Vatner
Dorothy E Vatner
Harvard University · US

Funding

Molecular Mechanisms in Chronically Stunned MyocardiumP01HL069020 · NHLBI · UNIV OF MED/DENT OF NJ-NJ MEDICAL SCHOOL · PI VATNER, DOROTHY EILEEN · 2001 to 2014
$21.3M
Longevity and Stress ResistanceP01AG027211 · NIA · UNIV OF MED/DENT OF NJ-NJ MEDICAL SCHOOL · PI VATNER, STEPHEN F · 2007 to 2013
$10.3M
CARDIOVASCULAR CONTROL IN NORMAL AND DISEASE STATESR01HL033107 · NHLBI · UNIV OF MED/DENT OF NJ-NJ MEDICAL SCHOOL · PI VATNER, STEPHEN F · 1985 to 2011
$6.2M
Role of Sgs1 DNA helicase in telomere maintenanceR01AG019719 · NIA · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI SINCLAIR, DAVID A. · 2001 to 2022
$5.3M
SIRT1 as a regulator of health and lifespan of mammalsR37AG028730 · NIA · HARVARD MEDICAL SCHOOL · PI SINCLAIR, DAVID A. · 2012 to 2021
$4.1M
Skeletal Muscle Basis for Improved Exercise Endurance in RGS14 KOR01HL106511 · NHLBI · UNIV OF MED/DENT OF NJ-NJ MEDICAL SCHOOL · PI VATNER, STEPHEN F · 2011 to 2019
$3.8M
Integrative Mechanisms in Cardiovascular DiseaseT32HL069752 · NHLBI · UNIV OF MED/DENT OF NJ-NJ MEDICAL SCHOOL · PI VATNER, STEPHEN F · 2004 to 2013
$2.9M
Intrinsic Vascular Smooth Muscle Cell StiffnessR01HL102472 · NHLBI · UNIV OF MED/DENT OF NJ-NJ MEDICAL SCHOOL · PI VATNER, STEPHEN F · 2010 to 2016
$2.5M
Adenylyl cyclase isoforms in hypertrophy and heart failureR01HL093481 · NHLBI · UNIV OF MED/DENT OF NJ-NJ MEDICAL SCHOOL · PI VATNER, STEPHEN F · 2009 to 2013
$2.3M
SFRP2, cell survival, and coronary vascular angiogenesisR01HL119464 · NHLBI · RBHS-NEW JERSEY MEDICAL SCHOOL · PI VATNER, DOROTHY EILEEN · 2013 to 2016
$1.8M
Rescue of Beta-Adrenergic Cardiomyopathy by Inhibition of Adenylyl CyclaseR01HL095888 · NHLBI · UNIV OF MED/DENT OF NJ-NJ MEDICAL SCHOOL · PI VATNER, DOROTHY EILEEN · 2009 to 2014
$1.7M
SIRT as a regulator of health and lifespan of mammalsR01AG028730 · NIA · HARVARD MEDICAL SCHOOL · PI SINCLAIR, DAVID A. · 2007 to 2011
$1.7M
NHLBI NIH HHS 1R01HL102472NHLBI NIH HHS 1R01HL106511NHLBI NIH HHS 5P01HL069020NHLBI NIH HHS 5R01HL033107NHLBI NIH HHS 5R01HL091781NHLBI NIH HHS 5R01HL093415NHLBI NIH HHS 5R01HL093481NHLBI NIH HHS 5R01HL095888NHLBI NIH HHS 5T32HL069752NHLBI NIH HHS P01 HL069020NHLBI NIH HHS R01 HL033107NHLBI NIH HHS R01 HL091781NHLBI NIH HHS R01 HL093415NHLBI NIH HHS R01 HL093481NHLBI NIH HHS R01 HL095888NHLBI NIH HHS R01 HL102472NHLBI NIH HHS R01 HL106511NHLBI NIH HHS R01 HL119464NHLBI NIH HHS R37 HL033107NHLBI NIH HHS T32 HL069752NIA NIH HHS 1R01AG019719NIA NIH HHS 5P01AG027211NIA NIH HHS 5R01AG028730NIA NIH HHS P01 AG027211NIA NIH HHS R01 AG019719NIA NIH HHS R01 AG023137NIA NIH HHS R01 AG028730NIA NIH HHS R01 AG028854NIA NIH HHS R37 AG028730
6 · The paper itself

Abstract

backgroundFor reasons that remain unclear, whether type 5 adenylyl cyclase (AC5), 1 of 2 major AC isoforms in heart, is protective or deleterious in response to cardiac stress is controversial. To reconcile this controversy we examined the cardiomyopathy induced by chronic isoproterenol in AC5 transgenic (Tg) mice and the signaling mechanisms involved. METHODS AND

resultsChronic isoproterenol increased oxidative stress and induced more severe cardiomyopathy in AC5 Tg, as left ventricular ejection fraction fell 1.9-fold more than wild type, along with greater left ventricular dilation and increased fibrosis, apoptosis, and hypertrophy. Oxidative stress induced by chronic isoproterenol, detected by 8-OhDG was 15% greater, P=0.007, in AC5 Tg hearts, whereas protein expression of manganese superoxide dismutase (MnSOD) was reduced by 38%, indicating that the susceptibility of AC5 Tg to cardiomyopathy may be attributable to decreased MnSOD expression. Consistent with this, susceptibility of the AC5 Tg to cardiomyopathy was suppressed by overexpression of MnSOD, whereas protection afforded by the AC5 knockout (KO) was lost in AC5 KO×MnSOD heterozyous KO mice. Elevation of MnSOD was eliminated by both sirtuin and MEK inhibitors, suggesting both the SIRT1/FoxO3a and MEK/ERK pathway are involved in MnSOD regulation by AC5.

conclusionsOverexpression of AC5 exacerbates the cardiomyopathy induced by chronic catecholamine stress by altering regulation of SIRT1/FoxO3a, MEK/ERK, and MnSOD, resulting in oxidative stress intolerance, thereby shedding light on new approaches for treatment of heart failure.

Indexed as

Adenylyl CyclasesAnimalsCardiomyopathiesCrosses, GeneticCyclic N-OxidesEnzyme InductionForkhead Box Protein O3Forkhead Transcription FactorsIsoproterenolMAP Kinase Signaling SystemMiceMice, KnockoutMice, TransgenicOxidative StressProtein Kinase InhibitorsSirtuin 1Adenylyl Cyclasesadenylyl cyclase type VCyclic N-OxidesForkhead Box Protein O3Forkhead Transcription FactorsFoxO3 protein, mouseIsoproterenolProtein Kinase InhibitorsSirt1 protein, mouseSirtuin 1Spin LabelsSuperoxide DismutaseSuperoxide Dismutase 2tempol

Identifiers

PMID23536361
PMCPMC3980473
OpenAlexW2103637973

What OpenQuestion holds

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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.