Unknown

Dataset Information

0

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


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 ?cyto- or ?cyto-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.

SUBMITTER: Olthoff JT 

PROVIDER: S-EPMC6269445 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

altmetric image

Publications

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

Olthoff John T JT   Lindsay Angus A   Abo-Zahrah Reem R   Baltgalvis Kristen A KA   Patrinostro Xiaobai X   Belanto Joseph J JJ   Yu Dae-Yeul DY   Perrin Benjamin J BJ   Garry Daniel J DJ   Rodney George G GG   Lowe Dawn A DA   Ervasti James M JM  

Nature communications 20181130 1


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.  ...[more]

Similar Datasets

| S-EPMC6234580 | biostudies-literature
| S-EPMC5474748 | biostudies-literature
| S-EPMC3822960 | biostudies-literature
| S-EPMC3287108 | biostudies-literature
| S-EPMC7582244 | biostudies-literature
| S-EPMC3006333 | biostudies-literature
| S-EPMC3459462 | biostudies-literature
| S-EPMC4989025 | biostudies-literature
| S-EPMC3963011 | biostudies-literature
| S-EPMC4088999 | biostudies-literature