Evidence map›Paper›PMID 28526910›Full record

ArticleBasic research in cardiology2017

Expression and regulation of type 2A protein phosphatases and alpha4 signalling in cardiac health and hypertrophy.

Olga Eleftheriadou, Andrii Boguslavskyi, Michael R Longman, Jonathan Cowan, Asvi Francois, Richard J Heads, Brian E Wadzinski, Ali Ryan, Michael J Shattock, Andrew K Snabaitis

Open access · hybridAbstract read
In one paragraph

Article in Basic research in cardiology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
0.7field-weighted citation impact, top 31% 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

11 citing papers in PubMed, 15 citations in OpenAlex.

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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 5 institutions in 2 countries.

Olga EleftheriadouSchool of Life Sciences, Pharmacy and Chemistry, Faculty of Science Engineering and Computing, Kingston University, Penrhyn Road, Kingston-upon-Thames, Surrey, KT1 2EE, UK.
Andrii BoguslavskyiCardiovascular Division, King's College London British Heart Foundation Centre, The Rayne Institute, St Thomas' Hospital, London, SE1 7EH, UK.
Michael R LongmanSchool of Life Sciences, Pharmacy and Chemistry, Faculty of Science Engineering and Computing, Kingston University, Penrhyn Road, Kingston-upon-Thames, Surrey, KT1 2EE, UK.
Jonathan CowanSchool of Life Sciences, Pharmacy and Chemistry, Faculty of Science Engineering and Computing, Kingston University, Penrhyn Road, Kingston-upon-Thames, Surrey, KT1 2EE, UK.
Asvi FrancoisCardiovascular Division, King's College London British Heart Foundation Centre, The Rayne Institute, St Thomas' Hospital, London, SE1 7EH, UK.
Richard J HeadsCardiovascular Division, King's College London British Heart Foundation Centre, The Rayne Institute, St Thomas' Hospital, London, SE1 7EH, UK.
Brian E WadzinskiDepartment of Pharmacology, Vanderbilt University, Nashville, TN, USA.
Ali RyanSchool of Life Sciences, Pharmacy and Chemistry, Faculty of Science Engineering and Computing, Kingston University, Penrhyn Road, Kingston-upon-Thames, Surrey, KT1 2EE, UK.
Michael J ShattockCardiovascular Division, King's College London British Heart Foundation Centre, The Rayne Institute, St Thomas' Hospital, London, SE1 7EH, UK.
Andrew K SnabaitisSchool of Life Sciences, Pharmacy and Chemistry, Faculty of Science Engineering and Computing, Kingston University, Penrhyn Road, Kingston-upon-Thames, Surrey, KT1 2EE, UK. a.snabaitis@kingston.ac.uk.
Kingston University · GBSt Thomas' Hospital · GBBritish Heart Foundation · GBKing's College London · GBVanderbilt University · US

Funding

British Heart Foundation FS/12/45/29647British Heart Foundation PG/14/73/30953British Heart Foundation RG/12/4/29426British Heart Foundation RG/17/15/33106
6 · The paper itself

Abstract

Cardiac physiology and hypertrophy are regulated by the phosphorylation status of many proteins, which is partly controlled by a poorly defined type 2A protein phosphatase-alpha4 intracellular signalling axis. Quantitative PCR analysis revealed that mRNA levels of the type 2A catalytic subunits were differentially expressed in H9c2 cardiomyocytes (PP2ACβ > PP2ACα > PP4C > PP6C), NRVM (PP2ACβ > PP2ACα = PP4C = PP6C), and adult rat ventricular myocytes (PP2ACα > PP2ACβ > PP6C > PP4C). Western analysis confirmed that all type 2A catalytic subunits were expressed in H9c2 cardiomyocytes; however, PP4C protein was absent in adult myocytes and only detectable following 26S proteasome inhibition. Short-term knockdown of alpha4 protein expression attenuated expression of all type 2A catalytic subunits. Pressure overload-induced left ventricular (LV) hypertrophy was associated with an increase in both PP2AC and alpha4 protein expression. Although PP6C expression was unchanged, expression of PP6C regulatory subunits (1) Sit4-associated protein 1 (SAP1) and (2) ankyrin repeat domain (ANKRD) 28 and 44 proteins was elevated, whereas SAP2 expression was reduced in hypertrophied LV tissue. Co-immunoprecipitation studies demonstrated that the interaction between alpha4 and PP2AC or PP6C subunits was either unchanged or reduced in hypertrophied LV tissue, respectively. Phosphorylation status of phospholemman (Ser63 and Ser68) was significantly increased by knockdown of PP2ACα, PP2ACβ, or PP4C protein expression. DNA damage assessed by histone H2A.X phosphorylation (γH2A.X) in hypertrophied tissue remained unchanged. However, exposure of cardiomyocytes to H

Indexed as

Signal TransductionAdaptor Proteins, Signal TransducingAnimalsAnimals, NewbornCell LineDNA DamageGene Expression Regulation, EnzymologicHistonesHypertrophy, Left VentricularIntercellular Signaling Peptides and ProteinsMembrane ProteinsMice, Inbred C57BLMolecular ChaperonesMyocytes, CardiacOxidative StressPhosphoprotein PhosphatasesAdaptor Proteins, Signal TransducingATP dependent 26S proteaseHistonesIgbp1 protein, mouseIntercellular Signaling Peptides and ProteinsMembrane ProteinsMolecular ChaperonesphospholemmanPhosphoprotein PhosphatasesPhosphoproteinsPpp2ca protein, ratProteasome Endopeptidase ComplexProtein Phosphatase 2protein phosphatase 4protein phosphatase 6Alpha4Cardiac hypertrophyH2A.XHydrogen peroxideType 2A protein phosphatase

Identifiers

PMID28526910
PMCPMC5438423
OpenAlexW2615357695

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.