Loss of peroxiredoxin-2 exacerbates eccentric contraction-induced force loss in dystrophin-deficient muscle

John T Olthoff, Angus Lindsay, Reem Abo-Zahrah, Kristen A. Baltgalvis, Xiaobai Patrinostro, Joseph J Belanto, Dae Yeul Yu, Benjamin J. Perrin, Daniel J Garry, George G. Rodney, Dawn A Lowe, James M Ervasti

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Force 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.

Original languageEnglish (US)
Article number5104
JournalNature communications
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2018

Fingerprint

Peroxiredoxins
Dystrophin
eccentrics
muscles
contraction
Muscle
NADPH Oxidase
Muscle Contraction
Muscles
Actins
Inbred mdx Mouse
Myoglobin
oxidase
Proteomics
Cysteine
Skeletal Muscle
Antioxidants
Wounds and Injuries
skeletal muscle
circuit breakers

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

Cite this

Loss of peroxiredoxin-2 exacerbates eccentric contraction-induced force loss in dystrophin-deficient muscle. / Olthoff, John T; Lindsay, Angus; Abo-Zahrah, Reem; Baltgalvis, Kristen A.; Patrinostro, Xiaobai; Belanto, Joseph J; Yu, Dae Yeul; Perrin, Benjamin J.; Garry, Daniel J; Rodney, George G.; Lowe, Dawn A; Ervasti, James M.

In: Nature communications, Vol. 9, No. 1, 5104, 01.12.2018.

Research output: Contribution to journalArticle

Olthoff, JT, Lindsay, A, Abo-Zahrah, R, Baltgalvis, KA, Patrinostro, X, Belanto, JJ, Yu, DY, Perrin, BJ, Garry, DJ, Rodney, GG, Lowe, DA & Ervasti, JM 2018, 'Loss of peroxiredoxin-2 exacerbates eccentric contraction-induced force loss in dystrophin-deficient muscle', Nature communications, vol. 9, no. 1, 5104. https://doi.org/10.1038/s41467-018-07639-3
Olthoff, John T ; Lindsay, Angus ; Abo-Zahrah, Reem ; Baltgalvis, Kristen A. ; Patrinostro, Xiaobai ; Belanto, Joseph J ; Yu, Dae Yeul ; Perrin, Benjamin J. ; Garry, Daniel J ; Rodney, George G. ; Lowe, Dawn A ; Ervasti, James M. / Loss of peroxiredoxin-2 exacerbates eccentric contraction-induced force loss in dystrophin-deficient muscle. In: Nature communications. 2018 ; Vol. 9, No. 1.
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