Evidence map›Paper›PMID 33712448›Full record

ArticleJournal of cell science2021

AMP-activated protein kinase is a key regulator of acute neurovascular permeability.

Silvia Dragoni, Bruna Caridi, Eleni Karatsai, Thomas Burgoyne, Mosharraf H Sarker, Patric Turowski

Open access · hybridAbstract read
In one paragraph

Article in Journal of cell science, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed, 1 pooled it
1.9field-weighted citation impact, top 16% 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

14 citing papers in PubMed, 1 synthesis or guideline pooled it, 17 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

6 authors at 1 institution in 1 country.

Silvia DragoniInstitute of Ophthalmology, University College London, 11-43 Bath Street, London EC1V 9EL, UK.
Bruna CaridiInstitute of Ophthalmology, University College London, 11-43 Bath Street, London EC1V 9EL, UK.
Eleni KaratsaiInstitute of Ophthalmology, University College London, 11-43 Bath Street, London EC1V 9EL, UK.
Thomas BurgoyneInstitute of Ophthalmology, University College London, 11-43 Bath Street, London EC1V 9EL, UK.
Mosharraf H SarkerInstitute of Ophthalmology, University College London, 11-43 Bath Street, London EC1V 9EL, UK.
Patric TurowskiInstitute of Ophthalmology, University College London, 11-43 Bath Street, London EC1V 9EL, UK.
University College London · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Many neuronal and retinal disorders are associated with pathological hyperpermeability of the microvasculature. We have used explants of rodent retinae to study acute neurovascular permeability, signal transduction and the role of AMP-activated protein kinase (AMPK). Following stimulation with either vascular endothelial growth factor (VEGF-A) or bradykinin (BK), AMPK was rapidly and strongly phosphorylated and acted as a key mediator of permeability downstream of Ca2+. Accordingly, AMPK agonists potently induced acute retinal vascular leakage. AMPK activation led to phosphorylation of endothelial nitric oxide synthase (eNOS, also known as NOS3), which in turn increased VE-cadherin (CDH5) phosphorylation on Y685. In parallel, AMPK also mediated phosphorylation of p38 MAP kinases (hereafter p38) and HSP27 (HSPB1), indicating that it regulated paracellular junctions and cellular contractility, both previously associated with endothelial permeability. Endothelial AMPK provided a missing link in neurovascular permeability, connecting Ca2+ transients to the activation of eNOS and p38, irrespective of the permeability-inducing factor used. Collectively, we find that, due to its compatibility with small molecule antagonists and agonists, as well as siRNA, the ex vivo retina model constitutes a reliable tool to identify and study regulators and mechanisms of acute neurovascular permeability.

Indexed as

AMP-Activated Protein KinasesVascular Endothelial Growth Factor APermeabilityPhosphorylationSignal TransductionAMP-Activated Protein KinasesVascular Endothelial Growth Factor AAMP-activated protein kinaseBradykininEndothelial nitric oxide synthaseRetinaVE-cadherinVEGF-A

Identifiers

PMID33712448
PMCPMC8077405
OpenAlexW3135825016

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.