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

dc.contributor.authorOlthoff, John T.
dc.contributor.authorLindsay, Angus
dc.contributor.authorAbo-Zahrah, Reem
dc.contributor.authorBaltgalvis, Kristen A.
dc.contributor.authorPatrinostro, Xiaobai
dc.contributor.authorBelanto, Joseph J.
dc.contributor.authorYu, Dae-Yeul
dc.contributor.authorPerrin, Benjamin J.
dc.contributor.authorGarry, Daniel J.
dc.contributor.authorRodney, George G.
dc.contributor.authorLowe, Dawn A.
dc.contributor.authorErvasti, James M.
dc.contributor.departmentBiology, School of Scienceen_US
dc.date.accessioned2019-05-23T18:21:56Z
dc.date.available2019-05-23T18:21:56Z
dc.date.issued2018-11-30
dc.description.abstractForce 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.en_US
dc.identifier.citationOlthoff, J. T., Lindsay, A., Abo-Zahrah, R., Baltgalvis, K. A., Patrinostro, X., Belanto, J. J., … Ervasti, J. M. (2018). Loss of peroxiredoxin-2 exacerbates eccentric contraction-induced force loss in dystrophin-deficient muscle. Nature communications, 9(1), 5104. doi:10.1038/s41467-018-07639-3en_US
dc.identifier.urihttps://hdl.handle.net/1805/19445
dc.language.isoen_USen_US
dc.publisherSpringer Natureen_US
dc.relation.isversionof10.1038/s41467-018-07639-3en_US
dc.relation.journalNature Communicationsen_US
dc.rightsAttribution-NonCommercial-NoDerivs 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/us/*
dc.sourcePMCen_US
dc.subjectDystrophinen_US
dc.subjectImmunoblottingen_US
dc.subjectImmunoprecipitationen_US
dc.subjectMuscle contractionen_US
dc.subjectPeroxiredoxinsen_US
dc.titleLoss of peroxiredoxin-2 exacerbates eccentric contraction-induced force loss in dystrophin-deficient muscleen_US
dc.typeArticleen_US
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