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Cholesterol removal from adult skeletal muscle impairs excitation–contraction coupling and aging reduces caveolin-3 and alters the expression of other triadic proteins

Overview of attention for article published in Frontiers in Physiology, April 2015
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Title
Cholesterol removal from adult skeletal muscle impairs excitation–contraction coupling and aging reduces caveolin-3 and alters the expression of other triadic proteins
Published in
Frontiers in Physiology, April 2015
DOI 10.3389/fphys.2015.00105
Pubmed ID
Authors

Genaro Barrientos, Paola Llanos, Jorge Hidalgo, Pura Bolaños, Carlo Caputo, Alexander Riquelme, Gina Sánchez, Andrew F. G. Quest, Cecilia Hidalgo

Abstract

Cholesterol and caveolin are integral membrane components that modulate the function/location of many cellular proteins. Skeletal muscle fibers, which have unusually high cholesterol levels in transverse tubules, express the caveolin-3 isoform but its association with transverse tubules remains contentious. Cholesterol removal impairs excitation-contraction (E-C) coupling in amphibian and mammalian fetal skeletal muscle fibers. Here, we show that treating single muscle fibers from adult mice with the cholesterol removing agent methyl-β-cyclodextrin decreased fiber cholesterol by 26%, altered the location pattern of caveolin-3 and of the voltage dependent calcium channel Cav1.1, and suppressed or reduced electrically evoked Ca(2+) transients without affecting membrane integrity or causing sarcoplasmic reticulum (SR) calcium depletion. We found that transverse tubules from adult muscle and triad fractions that contain ~10% attached transverse tubules, but not SR membranes, contained caveolin-3 and Cav1.1; both proteins partitioned into detergent-resistant membrane fractions highly enriched in cholesterol. Aging entails significant deterioration of skeletal muscle function. We found that triad fractions from aged rats had similar cholesterol and RyR1 protein levels compared to triads from young rats, but had lower caveolin-3 and glyceraldehyde 3-phosphate dehydrogenase and increased Na(+)/K(+)-ATPase protein levels. Both triad fractions had comparable NADPH oxidase (NOX) activity and protein content of NOX2 subunits (p47(phox) and gp91(phox)), implying that NOX activity does not increase during aging. These findings show that partial cholesterol removal impairs E-C coupling and alters caveolin-3 and Cav1.1 location pattern, and that aging reduces caveolin-3 protein content and modifies the expression of other triadic proteins. We discuss the possible implications of these findings for skeletal muscle function in young and aged animals.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 37 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Chile 2 5%
Unknown 35 95%

Demographic breakdown

Readers by professional status Count As %
Researcher 8 22%
Student > Master 6 16%
Professor > Associate Professor 5 14%
Professor 5 14%
Student > Ph. D. Student 5 14%
Other 6 16%
Unknown 2 5%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 11 30%
Agricultural and Biological Sciences 8 22%
Medicine and Dentistry 6 16%
Neuroscience 4 11%
Sports and Recreations 3 8%
Other 3 8%
Unknown 2 5%
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 17 April 2015.
All research outputs
#15,329,087
of 22,799,071 outputs
Outputs from Frontiers in Physiology
#6,651
of 13,562 outputs
Outputs of similar age
#157,200
of 264,200 outputs
Outputs of similar age from Frontiers in Physiology
#52
of 107 outputs
Altmetric has tracked 22,799,071 research outputs across all sources so far. This one is in the 22nd percentile – i.e., 22% of other outputs scored the same or lower than it.
So far Altmetric has tracked 13,562 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 47th percentile – i.e., 47% 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 264,200 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 31st percentile – i.e., 31% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 107 others from the same source and published within six weeks on either side of this one. This one is in the 49th percentile – i.e., 49% of its contemporaries scored the same or lower than it.