Alterations in the muscle force transfer apparatus in aged rats during unloading and reloading: impact of microRNA-31.

Autor: Hughes DC; Department of Neurobiology, Physiology and Behavior, University of California Davis, Davis, CA, USA., Marcotte GR; Department of Neurobiology, Physiology and Behavior, University of California Davis, Davis, CA, USA., Baehr LM; Department of Physiology and Membrane Biology, University of California Davis, Davis, CA, USA.; VA Northern California Health Care System, Mather, CA, USA., West DWD; Department of Physiology and Membrane Biology, University of California Davis, Davis, CA, USA.; VA Northern California Health Care System, Mather, CA, USA., Marshall AG; Department of Neurobiology, Physiology and Behavior, University of California Davis, Davis, CA, USA.; Department of Physiology and Membrane Biology, University of California Davis, Davis, CA, USA., Ebert SM; Department of Internal Medicine, University of Iowa, Iowa City, IA, USA.; Fraternal Order of Eagles Diabetes Research Center, University of Iowa, Iowa City, IA, USA.; Iowa City Veterans Affairs Medical Center, Iowa City, IA, USA., Davidyan A; Molecular, Cellular, and Integrative Physiology Graduate Group, University of California Davis, Davis, CA, USA., Adams CM; Department of Internal Medicine, University of Iowa, Iowa City, IA, USA.; Fraternal Order of Eagles Diabetes Research Center, University of Iowa, Iowa City, IA, USA.; Iowa City Veterans Affairs Medical Center, Iowa City, IA, USA., Bodine SC; Department of Neurobiology, Physiology and Behavior, University of California Davis, Davis, CA, USA.; Department of Physiology and Membrane Biology, University of California Davis, Davis, CA, USA.; VA Northern California Health Care System, Mather, CA, USA., Baar K; Department of Neurobiology, Physiology and Behavior, University of California Davis, Davis, CA, USA.; Department of Physiology and Membrane Biology, University of California Davis, Davis, CA, USA.; VA Northern California Health Care System, Mather, CA, USA.
Jazyk: angličtina
Zdroj: The Journal of physiology [J Physiol] 2018 Jul; Vol. 596 (14), pp. 2883-2900.
DOI: 10.1113/JP275833
Abstrakt: Key Points: Force transfer is integral for maintaining skeletal muscle structure and function. One important component is dystrophin. There is limited understanding of how force transfer is impacted by age and loading. Here, we investigate the force transfer apparatus in muscles of adult and old rats exposed to periods of disuse and reloading. Our results demonstrate an increase in dystrophin protein during the reloading phase in the adult tibialis anterior muscle that is delayed in the old muscle. The consequence of this delay is an increased susceptibility towards contraction-induced muscle injury. Central to the lack of dystrophin protein is an increase in miR-31, a microRNA that inhibits dystrophin translation. In vivo electroporation with a miR-31 sponge led to increased dystrophin protein and decreased contraction-induced muscle injury in old skeletal muscle. Overall, our results detail the importance of the force transfer apparatus and provide new mechanisms for contraction-induced injury in ageing skeletal muscle.
Abstract: In healthy muscle, the dystrophin-associated glycoprotein complex (DGC), the integrin/focal adhesion complex, intermediate filaments and Z-line proteins transmit force from the contractile proteins to the extracellular matrix. How loading and age affect these proteins is poorly understood. The experiments reported here sought to determine the effect of ageing on the force transfer apparatus following muscle unloading and reloading. Adult (9 months) and old (28 months) rats were subjected to 14 days of hindlimb unloading and 1, 3, 7 and 14 days of reloading. The DGC complex, intermediate filament and Z-line protein and mRNA levels, as well as dystrophin-targeting miRNAs (miR-31, -146b and -374) were examined in the tibialis anterior (TA) and medial gastrocnemius muscles at both ages. There was a significant increase in dystrophin protein levels (2.79-fold) upon 3 days of reloading in the adult TA muscle that did not occur in the old rats (P ≤ 0.05), and the rise in dystrophin protein occurred independent of dystrophin mRNA. The disconnect between dystrophin protein and mRNA levels can partially be explained by age-dependent differences in miR-31. The impaired dystrophin response in aged muscle was followed by an increase in other force transfer proteins (β-dystroglycan, desmuslin and LIM) that was not sufficient to prevent membrane disruption and muscle injury early in the reloading period. Inserting a miR-31 sponge increased dystrophin protein and decreased contraction-induced injury in the TA (P ≤ 0.05). Collectively, these data suggest that increased miR-31 with age contributes to an impaired dystrophin response and increased muscle injury after disuse.
(© 2018 The Authors. The Journal of Physiology © 2018 The Physiological Society.)
Databáze: MEDLINE
Externí odkaz: