Mitochondrial oxidative stress impairs contractile function but paradoxically increases muscle mass via fibre branching.
Fibre branching
Hyperplasia
Mitochondria
MnSOD
Reactive oxygen species
Skeletal muscle
Journal
Journal of cachexia, sarcopenia and muscle
ISSN: 2190-6009
Titre abrégé: J Cachexia Sarcopenia Muscle
Pays: Germany
ID NLM: 101552883
Informations de publication
Date de publication:
04 2019
04 2019
Historique:
received:
19
07
2018
accepted:
12
11
2018
pubmed:
2
2
2019
medline:
2
2
2019
entrez:
2
2
2019
Statut:
ppublish
Résumé
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 fibres 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 fibres (P < 0.05). Despite the increase in muscle mass of gastrocnemius and quadriceps, in situ sciatic nerve-stimulated isometric maximum-specific force (N/cm 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 fibre branching.
Sections du résumé
BACKGROUND
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.
METHODS
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 fibres 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.
RESULTS
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 fibres (P < 0.05). Despite the increase in muscle mass of gastrocnemius and quadriceps, in situ sciatic nerve-stimulated isometric maximum-specific force (N/cm
CONCLUSIONS
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 fibre branching.
Identifiants
pubmed: 30706998
doi: 10.1002/jcsm.12375
pmc: PMC6463475
doi:
Types de publication
Journal Article
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
411-428Subventions
Organisme : NIA NIH HHS
ID : R01 AG050676
Pays : United States
Organisme : NIGMS NIH HHS
ID : K12 GM111725
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG047879
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG050911
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG055395
Pays : United States
Organisme : NIGMS NIH HHS
ID : P20 GM103447
Pays : United States
Organisme : NIA NIH HHS
ID : T32 AG052363
Pays : United States
Organisme : NIGMS NIH HHS
ID : P30 GM114731
Pays : United States
Organisme : NIA NIH HHS
ID : P01 AG051442
Pays : United States
Commentaires et corrections
Type : ErratumIn
Informations de copyright
© 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.
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