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

Author

Listed:
  • John T. Olthoff

    (University of Minnesota)

  • Angus Lindsay

    (University of Minnesota)

  • Reem Abo-Zahrah

    (Baylor College of Medicine)

  • Kristen A. Baltgalvis

    (University of Minnesota)

  • Xiaobai Patrinostro

    (University of Minnesota)

  • Joseph J. Belanto

    (University of Minnesota)

  • Dae-Yeul Yu

    (Korea Research Institute of Bioscience and Biotechnology (KRIBB))

  • Benjamin J. Perrin

    (Indiana University-Purdue University Indianapolis)

  • Daniel J. Garry

    (University of Minnesota)

  • George G. Rodney

    (Baylor College of Medicine)

  • Dawn A. Lowe

    (University of Minnesota)

  • James M. Ervasti

    (University of Minnesota
    University of Minnesota)

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.

Suggested Citation

  • 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. Lo, 2018. "Loss of peroxiredoxin-2 exacerbates eccentric contraction-induced force loss in dystrophin-deficient muscle," Nature Communications, Nature, vol. 9(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-07639-3
    DOI: 10.1038/s41467-018-07639-3
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    Cited by:

    1. Yuan Zhou & Chen Zhang & Weidong Xiao & Roland W. Herzog & Renzhi Han, 2024. "Systemic delivery of full-length dystrophin in Duchenne muscular dystrophy mice," Nature Communications, Nature, vol. 15(1), pages 1-14, December.

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