lindsay-lossofperoxiredoxin-2018.pdf (2.57 MB)
Loss of peroxiredoxin-2 exacerbates eccentric contraction-induced force loss in dystrophin-deficient muscle
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posted on 2018-01-01, 00:00 authored by J T Olthoff, Angus Lindsay, R Abo-Zahrah, K A Baltgalvis, X Patrinostro, J J Belanto, D Y Yu, B J Perrin, D J Garry, G G Rodney, D A Lowe, J M ErvastiForce loss in skeletal muscle exposed to eccentric contraction is often attributed to injury. We show that EDL muscles from dystrophin-deficient mdx mice recover 65% of lost force within 120 min of eccentric contraction and exhibit minimal force loss when the interval between contractions is increased from 3 to 30 min. A proteomic screen of mdx muscle identified an 80% reduction in the antioxidant peroxiredoxin-2, likely due to proteolytic degradation following hyperoxidation by NADPH Oxidase 2. Eccentric contraction-induced force loss in mdx muscle was exacerbated by peroxiredoxin-2 ablation, and improved by peroxiredoxin-2 overexpression or myoglobin knockout. Finally, overexpression of γcyto- or βcyto-actin protects mdx muscle from eccentric contraction-induced force loss by blocking NADPH Oxidase 2 through a mechanism dependent on cysteine 272 unique to cytoplasmic actins. Our data suggest that eccentric contraction-induced force loss may function as an adaptive circuit breaker that protects mdx muscle from injurious contractions
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Journal
Nature CommunicationsVolume
9Article number
5104Pagination
1 - 14Publisher
NatureLocation
London, Eng.Publisher DOI
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eISSN
2041-1723Language
engPublication classification
C1 Refereed article in a scholarly journalUsage metrics
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