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The Role of P2Y Receptors in the Regulation of Atrophic Processes in Rat Skeletal Muscles under Unloading

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Abstract

Skeletal muscle atrophy during their unloading is due to a decrease in protein synthesis and an increase in proteolysis. The accumulation of ATP in muscle during unloading, detected at its early stages, may be one of the stimuli triggering this process. It has been shown that pannexin channels allow ATP efflux from the cytoplasm to the extracellular space during muscle unloading. Extracellular ATP can be sensed by P2Y2 receptors. To test the hypothesis on the involvement of P2Y2 receptors in the regulation of signaling processes in skeletal muscles at early stages of unloading, they were inhibited by their selective inhibitor AR-C 18925XX. The inhibition of P2Y2 receptors during 3-day unloading attenuated m. soleus atrophy, prevented ATP accumulation therein, downregulated the expression of MAFbx E3-ligase mRNA, ubiquitin and IL6 receptors, upregulated the level of AMPK phosphorylation and intensity of protein synthesis.

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Funding

This study was supported be the Russian Foundation for Basic Research (RFBR), grant no. 20-015-00138.

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Authors and Affiliations

  1. Institute of Biomedical Problems, Russian Academy of Sciences, Moscow, Russia

    K. А. Zaripova, S. P. Belova, B. S. Shenkman & T. L. Nemirovskaya

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  1. K. А. Zaripova
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  2. S. P. Belova
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  3. B. S. Shenkman
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  4. T. L. Nemirovskaya
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Contributions

Conceptualization, experimental design, writing and editing of the manuscript (L.N.T.); experimental design, data collection and processing, writing and editing of the manuscript (S.P.B.); data collection and processing, editing of the manuscript (K.A.Z.); general supervision (B.S.Sh.).

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Correspondence to T. L. Nemirovskaya.

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The authors declare that they have neither evident nor potential conflict of interest related to the publication of this article.

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Translated by A. Polyanovsky

Russian Text © The Author(s), 2022, published in Zhurnal Evolyutsionnoi Biokhimii i Fiziologii, 2022, Vol. 58, No. 6, pp. 487–497https://doi.org/10.31857/S0044452922060134.

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Zaripova, K.А., Belova, S.P., Shenkman, B.S. et al. The Role of P2Y Receptors in the Regulation of Atrophic Processes in Rat Skeletal Muscles under Unloading. J Evol Biochem Phys 58, 1708–1719 (2022). https://doi.org/10.1134/S0022093022060047

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