Reversible oxidative modifications partially cause myofibrillar active and passive force decline in early phase of immobilization
Year: 2025
Type: article
Abstract: Muscle immobilization leads to a decrease in muscle fiber size and contractile function, partly due to a decline in myofibrillar force. In this study, we examined the effects of reversible oxidative modifications on the decline of myofibrillar function during the early phase of immobilization. One leg of male C57BL6 mice was immobilized for 3 and 7 days, while contralateral leg was used as a non-treated (NT) control. After the given immobilization periods, mechanically skinned fibers were prepared from gastrocnemius muscle, and myofibrillar active and passive forces were assessed. Myofibrillar specific force decreased after 7 days of immobilization, although myofibrillar Ca2+ sensitivity remained unchanged. The decreased specific force was partially restored by a treatment with dithiothreitol (DTT), a reducing regent, only when applied to non-activated fibers, not activated fibers. Additionally, 3-morpholinosydnonimine (Sin-1) and peroxinitrite (ONOO-) decreased maximal force in non-activated fibers from NT but not immobilized (Im) muscles. Myofibrillar passive force decreased after 7 days of immobilization. DTT treatment increased passive force in both NT and Im fibers, with a greater improvement seen in Im fibers. Furthermore, treatment with oxidized glutathione prior to DTT treatment decreases passive force in both NT and Im fibers, with a greater reduction seen in NT fibers. These results suggest that reversible oxidative modifications partially contribute to the impairments in both myofibrillar active and passive forces, at least in the early phase of immobilization. Specifically, ONOO- and S-glutathionylation likely play an important role in active and passive force, respectively.
Authors: Daiki Watanabe, Takaaki Mishima, Taku Hamada
Institution: Osaka University of Health and Sport Sciences
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
OpenAlex ID: W4413636394