Chronic Ouabain Prevents Radiation-Induced Reduction in the α2 Na,K-ATPase Function in the Rat Diaphragm Muscle

The damaging effect of ionizing radiation (IR) on skeletal muscle Na,K-ATPase is an open field of research. Considering a therapeutic potential of ouabain, a specific ligand of the Na,K-ATPase, we tested its ability to protect against the IR-induced disturbances of Na,K-ATPase function in rat diaphr...

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Main Authors: Violetta V. Kravtsova, Arina A. Fedorova, Maria V. Tishkova, Alexandra A. Livanova, Oleg V. Vetrovoy, Alexander G. Markov, Vladimir V. Matchkov, Igor I. Krivoi
Format: Article
Language:English
Published: MDPI AG 2022-09-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/23/18/10921
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author Violetta V. Kravtsova
Arina A. Fedorova
Maria V. Tishkova
Alexandra A. Livanova
Oleg V. Vetrovoy
Alexander G. Markov
Vladimir V. Matchkov
Igor I. Krivoi
author_facet Violetta V. Kravtsova
Arina A. Fedorova
Maria V. Tishkova
Alexandra A. Livanova
Oleg V. Vetrovoy
Alexander G. Markov
Vladimir V. Matchkov
Igor I. Krivoi
author_sort Violetta V. Kravtsova
collection DOAJ
description The damaging effect of ionizing radiation (IR) on skeletal muscle Na,K-ATPase is an open field of research. Considering a therapeutic potential of ouabain, a specific ligand of the Na,K-ATPase, we tested its ability to protect against the IR-induced disturbances of Na,K-ATPase function in rat diaphragm muscle that co-expresses the α1 and α2 isozymes of this protein. Male Wistar rats (<i>n</i> = 26) were subjected to 6-day injections of vehicle (0.9% NaCl) or ouabain (1 µg/kg/day). On the fourth day of injections, rats were exposed to one-time total-body X-ray irradiation (10 Gy), or a sham irradiation. The isolated muscles were studied 72 h post-irradiation. IR decreased the electrogenic contribution of the α2 Na,K-ATPase without affecting its protein content, thereby causing sarcolemma depolarization. IR increased serum concentrations of ouabain, IL-6, and corticosterone, decreased lipid peroxidation, and changed cellular redox status. Chronic ouabain administration prevented IR-induced depolarization and loss of the α2 Na,K-ATPase electrogenic contribution without changing its protein content. This was accompanied with an elevation of ouabain concentration in circulation and with the lack of IR-induced suppression of lipid peroxidation. Given the crucial role of Na,K-ATPase in skeletal muscle performance, these findings may have therapeutic implications as countermeasures for IR-induced muscle pathology.
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spelling doaj.art-d5f1cbb0f6414a38a915d2ebadcd63472023-11-23T16:50:33ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-09-0123181092110.3390/ijms231810921Chronic Ouabain Prevents Radiation-Induced Reduction in the α2 Na,K-ATPase Function in the Rat Diaphragm MuscleVioletta V. Kravtsova0Arina A. Fedorova1Maria V. Tishkova2Alexandra A. Livanova3Oleg V. Vetrovoy4Alexander G. Markov5Vladimir V. Matchkov6Igor I. Krivoi7Department of General Physiology, St. Petersburg State University, 199034 St. Petersburg, RussiaDepartment of General Physiology, St. Petersburg State University, 199034 St. Petersburg, RussiaDepartment of General Physiology, St. Petersburg State University, 199034 St. Petersburg, RussiaDepartment of General Physiology, St. Petersburg State University, 199034 St. Petersburg, RussiaPavlov Institute of Physiology, Russian Academy of Sciences, 199034 St. Petersburg, RussiaDepartment of General Physiology, St. Petersburg State University, 199034 St. Petersburg, RussiaDepartment of Biomedicine, Aarhus University, C 8000 Aarhus, DenmarkDepartment of General Physiology, St. Petersburg State University, 199034 St. Petersburg, RussiaThe damaging effect of ionizing radiation (IR) on skeletal muscle Na,K-ATPase is an open field of research. Considering a therapeutic potential of ouabain, a specific ligand of the Na,K-ATPase, we tested its ability to protect against the IR-induced disturbances of Na,K-ATPase function in rat diaphragm muscle that co-expresses the α1 and α2 isozymes of this protein. Male Wistar rats (<i>n</i> = 26) were subjected to 6-day injections of vehicle (0.9% NaCl) or ouabain (1 µg/kg/day). On the fourth day of injections, rats were exposed to one-time total-body X-ray irradiation (10 Gy), or a sham irradiation. The isolated muscles were studied 72 h post-irradiation. IR decreased the electrogenic contribution of the α2 Na,K-ATPase without affecting its protein content, thereby causing sarcolemma depolarization. IR increased serum concentrations of ouabain, IL-6, and corticosterone, decreased lipid peroxidation, and changed cellular redox status. Chronic ouabain administration prevented IR-induced depolarization and loss of the α2 Na,K-ATPase electrogenic contribution without changing its protein content. This was accompanied with an elevation of ouabain concentration in circulation and with the lack of IR-induced suppression of lipid peroxidation. Given the crucial role of Na,K-ATPase in skeletal muscle performance, these findings may have therapeutic implications as countermeasures for IR-induced muscle pathology.https://www.mdpi.com/1422-0067/23/18/10921ionizing radiationskeletal muscleNa,K-ATPase isozymesouabainresting membrane potential
spellingShingle Violetta V. Kravtsova
Arina A. Fedorova
Maria V. Tishkova
Alexandra A. Livanova
Oleg V. Vetrovoy
Alexander G. Markov
Vladimir V. Matchkov
Igor I. Krivoi
Chronic Ouabain Prevents Radiation-Induced Reduction in the α2 Na,K-ATPase Function in the Rat Diaphragm Muscle
International Journal of Molecular Sciences
ionizing radiation
skeletal muscle
Na,K-ATPase isozymes
ouabain
resting membrane potential
title Chronic Ouabain Prevents Radiation-Induced Reduction in the α2 Na,K-ATPase Function in the Rat Diaphragm Muscle
title_full Chronic Ouabain Prevents Radiation-Induced Reduction in the α2 Na,K-ATPase Function in the Rat Diaphragm Muscle
title_fullStr Chronic Ouabain Prevents Radiation-Induced Reduction in the α2 Na,K-ATPase Function in the Rat Diaphragm Muscle
title_full_unstemmed Chronic Ouabain Prevents Radiation-Induced Reduction in the α2 Na,K-ATPase Function in the Rat Diaphragm Muscle
title_short Chronic Ouabain Prevents Radiation-Induced Reduction in the α2 Na,K-ATPase Function in the Rat Diaphragm Muscle
title_sort chronic ouabain prevents radiation induced reduction in the α2 na k atpase function in the rat diaphragm muscle
topic ionizing radiation
skeletal muscle
Na,K-ATPase isozymes
ouabain
resting membrane potential
url https://www.mdpi.com/1422-0067/23/18/10921
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