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Mitochondrial ATP Depletion Disrupts Caco-2 Monolayer Integrity and Internalizes Claudin 7

Overview of attention for article published in Frontiers in Physiology, October 2017
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Title
Mitochondrial ATP Depletion Disrupts Caco-2 Monolayer Integrity and Internalizes Claudin 7
Published in
Frontiers in Physiology, October 2017
DOI 10.3389/fphys.2017.00794
Pubmed ID
Authors

Lonneke M. JanssenDuijghuijsen, Sander Grefte, Vincent C. J. de Boer, Lara Zeper, Dorien A. M. van Dartel, Inge van der Stelt, Melissa Bekkenkamp-Grovenstein, Klaske van Norren, Harry J. Wichers, Jaap Keijer

Abstract

Objective:In vivo studies suggest that intestinal barrier integrity is dependent on mitochondrial ATP production. Here, we aim to provide mechanistic support, using an in vitro model mimicking the oxidative in vivo situation. Methods: Human Caco-2 cells were cultured for 10 days in culture flasks or for 14 days on transwell inserts in either glucose-containing or galactose-containing medium. Mitochondria were visualized and cellular respiration and levels of oxidative phosphorylation (OXPHOS) proteins were determined. Mitochondrial ATP depletion was induced using CCCP, rotenone, or piericidin A (PA). Monolayer permeability was assessed using transepithelial electrical resistance (TEER) and fluorescein flux. Gene expression and cellular distribution of tight junction proteins were analyzed. Results: Caco-2 cells cultured in galactose-containing, but not in glucose-containing, medium showed increased mitochondrial connectivity, oxygen consumption rates and levels of OXPHOS proteins. Inhibition of mitochondrial ATP production using CCCP, rotenone or PA resulted in a dose-dependent increase in Caco-2 monolayer permeability. In-depth studies with PA showed a six fold decrease in cellular ATP and revealed increased gene expression of tight junction proteins (TJP) 1 and 2, occludin, and claudin 1, but decreased gene expression of claudin 2 and 7. Of these, claudin 7 was clearly redistributed from the cellular membrane into the cytoplasm, while the others were not (TJP1, occludin) or slightly (claudin 2, actin) affected. In vivo studies suggest that intestinal barrier integrity is dependent on mitochondrial ATP production. Here, we aim to provide mechanistic support, using an in vitro model mimicking the oxidative in vivo situation. Conclusions: Well-functioning mitochondria are essential for maintaining cellular energy status and monolayer integrity of galactose grown Caco-2 cells. Energy depletion-induced Caco-2 monolayer permeability may be facilitated by changes in the distribution of claudin 7.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 71 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 71 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 15 21%
Student > Bachelor 15 21%
Student > Master 9 13%
Researcher 3 4%
Student > Doctoral Student 2 3%
Other 7 10%
Unknown 20 28%
Readers by discipline Count As %
Agricultural and Biological Sciences 12 17%
Biochemistry, Genetics and Molecular Biology 11 15%
Immunology and Microbiology 5 7%
Medicine and Dentistry 5 7%
Engineering 4 6%
Other 13 18%
Unknown 21 30%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 28 October 2017.
All research outputs
#18,573,839
of 23,005,189 outputs
Outputs from Frontiers in Physiology
#8,221
of 13,760 outputs
Outputs of similar age
#248,713
of 324,711 outputs
Outputs of similar age from Frontiers in Physiology
#204
of 320 outputs
Altmetric has tracked 23,005,189 research outputs across all sources so far. This one is in the 11th percentile – i.e., 11% of other outputs scored the same or lower than it.
So far Altmetric has tracked 13,760 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 7.6. This one is in the 31st percentile – i.e., 31% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 324,711 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 12th percentile – i.e., 12% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 320 others from the same source and published within six weeks on either side of this one. This one is in the 30th percentile – i.e., 30% of its contemporaries scored the same or lower than it.