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Chronic sustained hypoxia-induced redox remodeling causes contractile dysfunction in mouse sternohyoid muscle

Overview of attention for article published in Frontiers in Physiology, April 2015
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Title
Chronic sustained hypoxia-induced redox remodeling causes contractile dysfunction in mouse sternohyoid muscle
Published in
Frontiers in Physiology, April 2015
DOI 10.3389/fphys.2015.00122
Pubmed ID
Authors

Philip Lewis, David Sheehan, Renata Soares, Ana Varela Coelho, Ken D. O'Halloran

Abstract

Chronic sustained hypoxia (CH) induces structural and functional adaptations in respiratory muscles of animal models, however the underlying molecular mechanisms are unclear. This study explores the putative role of CH-induced redox remodeling in a translational mouse model, with a focus on the sternohyoid-a representative upper airway dilator muscle involved in the control of pharyngeal airway caliber. We hypothesized that exposure to CH induces redox disturbance in mouse sternohyoid muscle in a time-dependent manner affecting metabolic capacity and contractile performance. C57Bl6/J mice were exposed to normoxia or normobaric CH (FiO2 = 0.1) for 1, 3, or 6 weeks. A second cohort of animals was exposed to CH for 6 weeks with and without antioxidant supplementation (tempol or N-acetyl cysteine in the drinking water). Following CH exposure, we performed 2D redox proteomics with mass spectrometry, metabolic enzyme activity assays, and cell-signaling assays. Additionally, we assessed isotonic contractile and endurance properties ex vivo. Temporal changes in protein oxidation and glycolytic enzyme activities were observed. Redox modulation of sternohyoid muscle proteins key to contraction, metabolism and cellular homeostasis was identified. There was no change in redox-sensitive proteasome activity or HIF-1α content, but CH decreased phospho-JNK content independent of antioxidant supplementation. CH was detrimental to sternohyoid force- and power-generating capacity and this was prevented by chronic antioxidant supplementation. We conclude that CH causes upper airway dilator muscle dysfunction due to redox modulation of proteins key to function and homeostasis. Such changes could serve to further disrupt respiratory homeostasis in diseases characterized by CH such as chronic obstructive pulmonary disease. Antioxidants may have potential use as an adjunctive therapy in hypoxic respiratory disease.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 31 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 31 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 6 19%
Student > Master 5 16%
Researcher 3 10%
Student > Bachelor 3 10%
Professor > Associate Professor 3 10%
Other 3 10%
Unknown 8 26%
Readers by discipline Count As %
Medicine and Dentistry 7 23%
Agricultural and Biological Sciences 4 13%
Biochemistry, Genetics and Molecular Biology 2 6%
Sports and Recreations 2 6%
Nursing and Health Professions 1 3%
Other 5 16%
Unknown 10 32%
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 06 May 2015.
All research outputs
#18,405,972
of 22,799,071 outputs
Outputs from Frontiers in Physiology
#8,105
of 13,562 outputs
Outputs of similar age
#193,192
of 264,968 outputs
Outputs of similar age from Frontiers in Physiology
#64
of 106 outputs
Altmetric has tracked 22,799,071 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 13,562 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 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 264,968 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 15th percentile – i.e., 15% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 106 others from the same source and published within six weeks on either side of this one. This one is in the 33rd percentile – i.e., 33% of its contemporaries scored the same or lower than it.