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Ahn 2019 J Cachexia Sarcopenia Muscle
Additional label 2019-02  + , Amplex UltraRed  +
Coupling states OXPHOS  + , LEAK  +
Has abstract Excess reactive oxygen species (ROS) and m
Excess reactive oxygen species (ROS) and muscle weakness occur in parallel in multiple pathological conditions. However, the causative role of skeletal muscle mitochondrial ROS (mtROS) on neuromuscular junction (NMJ) morphology and function and muscle weakness has not been directly investigated. We generated mice lacking skeletal muscle-specific manganese-superoxide dismutase (mSod2KO) to increase mtROS using a cre-Lox approach driven by human skeletal actin. We determined primary functional parameters of skeletal muscle mitochondrial function (respiration, ROS, and calcium retention capacity) using permeabilized muscle fibers and isolated muscle mitochondria. We assessed contractile properties of isolated skeletal muscle using ''in situ'' and ''in vitro'' preparations and whole lumbrical muscles to elucidate the mechanisms of contractile dysfunction. The mSod2KO mice, contrary to our prediction, exhibit a 10-15% increase in muscle mass associated with an ~50% increase in central nuclei and ~35% increase in branched fibers (P < 0.05). Despite the increase in muscle mass of ''gastrocnemius'' and ''quadriceps'', in situ sciatic nerve-stimulated isometric maximum-specific force (N/cm<sup>2</sup>), force per cross-sectional area, is impaired by ~60% and associated with increased NMJ fragmentation and size by ~40% (P < 0.05). Intrinsic alterations of components of the contractile machinery show elevated markers of oxidative stress, for example, lipid peroxidation is increased by ~100%, oxidized glutathione is elevated by ~50%, and oxidative modifications of myofibrillar proteins are increased by ~30% (P < 0.05). We also find an approximate 20% decrease in the intracellular calcium transient that is associated with specific force deficit. Excess superoxide generation from the mitochondrial complexes causes a deficiency of succinate dehydrogenase and reduced complex-II-mediated respiration and adenosine triphosphate generation rates leading to severe exercise intolerance (~10 min vs. ~2 h in wild type, P < 0.05). Increased skeletal muscle mtROS is sufficient to elicit NMJ disruption and contractile abnormalities, but not muscle atrophy, suggesting new roles for mitochondrial oxidative stress in maintenance of muscle mass through increased fiber branching. <small>© 2019 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of the Society on Sarcopenia, Cachexia and Wasting Disorders.</small>
hexia and Wasting Disorders.</small>  +
Has editor [[Plangger M]]  +
Has info [ PMID: 30706998 Open Access]  +
Has publicationkeywords Hyperplasia  + , Mitochondria  + , MnSOD  + , Reactive oxygen species  + , Skeletal muscle  + , Fiber branching  +
Has title Ahn B, Ranjit R, Premkumar P, Pharaoh G, P
Ahn B, Ranjit R, Premkumar P, Pharaoh G, Piekarz KM, Matsuzaki S, Claflin DR, Riddle K, Judge J, Bhaskaran S, Satara Natarajan K, Barboza E, Wronowski B, Kinter M, Humphries KM, Griffin TM, Freeman WM, Richardson A, Brooks SV, Van Remmen H (2019) Mitochondrial oxidative stress impairs contractile function but paradoxically increases muscle mass via fiber branching. J Cachexia Sarcopenia Muscle 10:411-28.
g. J Cachexia Sarcopenia Muscle 10:411-28.  +
Instrument and method Oxygraph-2k  + , O2k-Fluorometer  +
Mammal and model Mouse  +
MiP area Respiration  + , Genetic knockout;overexpression  +
Pathways N  + , S  + , CIV  + , NS  + , ROX  +
Preparation Isolated mitochondria  +
Respiration and regulation ATP production  +
Stress Oxidative stress;RONS  +
Tissue and cell Skeletal muscle  +
Was published by MiPNetLab US OK Oklahoma City Van Remmen H +
Was published in journal J Cachexia Sarcopenia Muscle +
Was published in year 2019  +
Was written by Ahn B + , Ranjit R + , Premkumar P + , Pharaoh G + , Piekarz KM + , Matsuzaki S + , Claflin DR + , Riddle K + , Judge J + , Bhaskaran S + , Satara Natarajan K + , Barboza E + , Wronowski B + , Kinter M + , Humphries KM + , Griffin TM + , Freeman WM + , Richardson A + , Brooks SV + , Van Remmen H +
Categories Publications
Modification date
"Modification date" is a predefined property that corresponds to the date of the last modification of a subject and is provided by Semantic MediaWiki.
12:47:34, 23 May 2019  +
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