Force generated by myosin cross-bridges is reduced in myofibrils exposed to ROS/RNSShow others and affiliations
2019 (English)In: American Journal of Physiology - Cell Physiology, ISSN 0363-6143, E-ISSN 1522-1563, Vol. 317, no 6, p. C1304-C1312Article in journal (Refereed) Published
Abstract [en]
Skeletal muscle weakness is associated with oxidative stress and oxidative posttranslational modifications on contractile proteins. There is indirect evidence that reactive oxygen/nitrogen species (ROS/RNS) affect skeletal muscle myofibrillar function, although the details of the acute effects of ROS/RNS on myosin-actin interactions are not known. In this study. we examined the effects of peroxynitrite (ONOO-) on the contractile properties of individual skeletal muscle myofibrils by monitoring myofibril-induced displacements of an atomic force cantilever upon activation and relaxation. The isometric force decreased by similar to 50% in myofibrils treated with the ONOO- donor (SIN-1) or directly with ONOO-. which was independent of the cross-bridge abundancy condition (i.e., rigor or relaxing condition) during SIN-1 or ONOO- treatment. The force decrease was attributed to an increase in the cross-bridge detachment rate (g(app)) in combination with a conservation of the force redevelopment rate (k(Tr)) and hence, an increase in the population of cross-bridges transitioning from force-generating to non-force-generating cross-bridges during steady-state. Taken together, the results of this study provide important information on how ROS/RNS affect myofibrillar force production which may be of importance for conditions where increased oxidative stress is part of the pathophysiology.
Place, publisher, year, edition, pages
American Physiological Society , 2019. Vol. 317, no 6, p. C1304-C1312
Keywords [en]
cross-bridges, myofibrils, oxidative stress, peroxynitrite, skeletal muscle, SKELETAL-MUSCLE FIBERS, REACTIVE OXYGEN, CONTRACTILE DYSFUNCTION, INORGANIC-PHOSPHATE, STRIATED-MUSCLE, ACTIVATION, DIAPHRAGM, PEROXIDE, KINETICS
National Category
Physiology
Identifiers
URN: urn:nbn:se:oru:diva-99345DOI: 10.1152/ajpcell.00272.2019ISI: 000500920700013PubMedID: 31553646Scopus ID: 2-s2.0-85076331562OAI: oai:DiVA.org:oru-99345DiVA, id: diva2:1663348
Funder
Swedish Research CouncilSwedish Rheumatism Association
Note
Funding agency:
Canadian Institutes of Health Research (CIHR)
2022-06-022022-06-022022-06-09Bibliographically approved