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Contribution of SERCA Activity to Contractile Properties of the Rat Soleus Muscle during One-Week Unloading

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Abstract

Dysfunction of skeletal muscles and their atrophy under unloading are accompanied by excess calcium accumulation in the myoplasm of muscle fibers. We hypothesized that calcium accumulation may occur, among other reasons, due to inhibition of SERCA activity under muscle unloading. In this case, the use of a sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) activator would reduce the calcium level in the myoplasm and prevent the consequences of unloading. Male Wistar rats were divided into 3 groups: vivarium control with placebo administration (C, n = 8), 7-day suspension group with placebo administration (7HS, n = 8), and 7-day suspension group with intraperitoneal administration of the SERCA activator CDN1163 (7HS + CDN, 50 mg/kg, n = 8). One m. soleus of each rat was frozen in liquid nitrogen, the second was tested for functional properties. 7HS rats demonstrated an increased m. soleus fatigue in the ex vivo test, a significant increase in mRNA and the number of fast-twitch muscle fibers, an increase in the level of calcium-dependent CaMK II phosphorylation and tropomyosin oxidation, as well as a decrease in mitochondrial DNA and protein levels. All these changes were prevented in the 7HS + CDN group administered with SERCA activator. Conclusion: 7-day SERCA activator administration does not delay m. soleus atrophy but prevents the development of its fatigue, probably due to prevention of a reduction in the number of type I fibers and mitochondrial biogenesis markers.

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Funding

This work was supported by the Russian Science Foundation, grant no. 21-15-00228.

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Authors and Affiliations

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Contributions

K.A.Z.—conducting experiments with animals, isolating and sampling proteins and RNA, running electrophoreses, blots and PCR, statistical data processing; S.P.B.—general organization of experiments, isolating and sampling proteins and RNA, running electrophoreses, blots and PCR, statistical data processing, discussing the results; K.A.Sh.—general organization of experiments, isolating and sampling proteins and RNA, running electrophoreses, blots and PCR, statistical data processing, discussing the results; S.A.T.—studying m. soleus functional properties; I.D.L.—running electrophoreses, blots and PCR, statistical data processing; T.L.N.—experimental design, discussing the results, writing a paper.

Corresponding author

Correspondence to T. L. Nemirovskaya.

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COMPLIANCE WITH ETHICAL STANDARDS

All applicable international, national and/or institutional guidelines for the care and use of animals have been followed. All experimental procedures performed with the involvement of animals complied with the ethical standards approved by the legal acts of the Russian Federation, the principles of the Basel Declaration, and the recommendations by the Biomedical Ethics Committee at the Institute of Biomedical Problems of the Russian Academy of Sciences (Meeting minutes No. 584, dated May 31, 2021).

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The authors declare that they have no conflict of interest.

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Translated by A. Polyanovsky

Russian Text © The Author(s), 2023, published in Rossiiskii Fiziologicheskii Zhurnal imeni I.M. Sechenova, 2023, Vol. 109, No. 7, pp. 872–889https://doi.org/10.31857/S0869813923070117.

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Sharlo, K.A., Lvova, I.D., Tyganov, S.A. et al. Contribution of SERCA Activity to Contractile Properties of the Rat Soleus Muscle during One-Week Unloading. J Evol Biochem Phys 59, 1237–1251 (2023). https://doi.org/10.1134/S0022093023040178

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