Evidence map›Paper›PMID 26869446›Full record

ArticleBiochimica et biophysica acta2016

Linoleic acid permeabilizes gastric epithelial cells by increasing connexin 43 levels in the cell membrane via a GPR40- and Akt-dependent mechanism.

Carlos Puebla, Bruno A Cisterna, Daniela P Salas, Fernando Delgado-López, Paul D Lampe, Juan C Sáez

Open access · greenAbstract read
In one paragraph

Article in Biochimica et biophysica acta, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
1.7field-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

20 citing papers in PubMed, 26 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 4 institutions in 2 countries.

Carlos PueblaDepartamento de Fisiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile. Electronic address: capuebla@uc.cl.
Bruno A CisternaDepartamento de Fisiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile; Instituto Milenio, Centro Interdisciplinario de Neurociencias de Valparaíso, Universidad de Valparaíso, Valparaíso, Chile.
Daniela P SalasDepartamento de Fisiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile.
Fernando Delgado-LópezLaboratorios de Biomedicina, Departamento de Ciencias Preclínicas, Facultad de Medicina, Universidad Católica del Maule, Talca, Chile.
Paul D LampeTranslational Research Program, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, United States.
Juan C SáezDepartamento de Fisiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile; Instituto Milenio, Centro Interdisciplinario de Neurociencias de Valparaíso, Universidad de Valparaíso, Valparaíso, Chile. Electronic address: jsaez@bio.puc.cl.
Pontificia Universidad Católica de Chile · CLCatholic University of the Maule · CLFred Hutch Cancer Center · USUniversity of Valparaíso · CL

Funding

PHOSPHORYLATION OF GAP JUNCTION PROTEINSR01GM055632 · NIGMS · FRED HUTCHINSON CANCER RESEARCH CENTER · PI LAMPE, PAUL D. · 1997 to 2017
$6.1M
NIGMS NIH HHS GM55632NIGMS NIH HHS R01 GM055632
6 · The paper itself

Abstract

Linoleic acid (LA) is known to activate G-protein coupled receptors and connexin hemichannels (Cx HCs) but possible interlinks between these two responses remain unexplored. Here, we evaluated the mechanism of action of LA on the membrane permeability mediated by Cx HCs in MKN28 cells. These cells were found to express connexins, GPR40, GPR120, and CD36 receptors. The Cx HC activity of these cells increased after 5 min of treatment with LA or GW9508, an agonist of GPR40/GPR120; or exposure to extracellular divalent cation-free solution (DCFS), known to increase the open probability of Cx HCs, yields an immediate increase in Cx HC activity of similar intensity and additive with LA-induced change. Treatment with a CD36 blocker or transfection with siRNA-GPR120 maintains the LA-induced Cx HC activity. However, cells transfected with siRNA-GPR40 did not show LA-induced Cx HC activity but activity was increased upon exposure to DCFS, confirming the presence of activatable Cx HCs in the cell membrane. Treatment with AKTi (Akt inhibitor) abrogated the LA-induced Cx HC activity. In HeLa cells transfected with Cx43 (HeLa-Cx43), LA induced phosphorylation of surface Cx43 at serine 373 (S373), site for Akt phosphorylation. HeLa-Cx43 but not HeLa-Cx43 cells with a S373A mutation showed a LA-induced Cx HC activity directly related to an increase in cell surface Cx43 levels. Thus, the increase in membrane permeability induced by LA is mediated by an intracellular signaling pathway activated by GPR40 that leads to an increase in membrane levels of Cx43 phosphorylated at serine 373 via Akt.

Indexed as

CalciumCell MembraneCell Membrane PermeabilityConnexin 43Epithelial CellsGastric MucosaHeLa CellsHumansLinoleic AcidPhosphorylationProtein Kinase InhibitorsProto-Oncogene Proteins c-aktReceptors, G-Protein-CoupledRNA InterferenceSerineSignal TransductionCalciumConnexin 43FFAR1 protein, humanGJA1 protein, humanGJA1 protein, mouseGja1 protein, ratLinoleic AcidProtein Kinase InhibitorsProto-Oncogene Proteins c-aktReceptors, G-Protein-CoupledSerineAkt kinase, G protein-coupled receptor (GPCR)Connexon (hemichannel)FFAR1Polyunsaturated fatty acid (PUFA)Protein phosphorylationTransmembrane permeability

Identifiers

PMID26869446
PMCPMC4821727
OpenAlexW2271435922

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.