TY - JOUR

T1 - Chronic Ouabain Prevents Radiation-Induced Reduction in the α2 Na,K-ATPase Function in the Rat Diaphragm Muscle

AU - Кравцова, Виолетта Васильевна

AU - Федорова, Арина Александровна

AU - Тишкова, Мария Вячеславовна

AU - Ливанова, Александра Андреевна

AU - Ветровой, Олег Васильевич

AU - Марков, Александр Георгиевич

AU - Мачков, Владимир

AU - Кривой, Игорь Ильич

N1 - Publisher Copyright: © 2022 by the authors.

PY - 2022/9/18

Y1 - 2022/9/18

N2 - 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 (n = 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.

AB - 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 (n = 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.

KW - ионизирующее излучение

KW - скелетная мышца

KW - натрий-калиевый насос

KW - уабаин

KW - потенциал покоя

KW - Na,K-ATPase isozymes

KW - ionizing radiation

KW - ouabain

KW - resting membrane potential

KW - skeletal muscle

KW - Rats, Wistar

KW - Rats

KW - Male

KW - Muscle, Skeletal/metabolism

KW - Sodium/metabolism

KW - Diaphragm/metabolism

KW - Ouabain/metabolism

KW - Animals

KW - Saline Solution

KW - Corticosterone/metabolism

KW - Interleukin-6/metabolism

KW - Sodium-Potassium-Exchanging ATPase/metabolism

KW - Ligands

KW - Isoenzymes/metabolism

UR - http://www.scopus.com/inward/record.url?scp=85138382590&partnerID=8YFLogxK

UR - https://www.mendeley.com/catalogue/b6d0a293-62d8-3663-b846-0f43d99afb0b/

U2 - 10.3390/ijms231810921

DO - 10.3390/ijms231810921

M3 - Article

C2 - 36142836

VL - 23

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1422-0067

IS - 18

M1 - 10921

ER -