Abstract: The imbalance in the ratio of protein synthesis versus protein degradation results in skeletal muscle atrophy following unloading. Theonset of these processes is regulated by the sarcoplasmic concentrations of ATP and calcium (Ca 2 þ ). We tested the hypothesis thatunloading-induced inactivation of sarcoendoplasmic reticulum calcium ATPase (SERCA) results in raised Ca2 þ concentrations, trigger-ing catabolic processes. CDN1163, an activator of SERCA, was used to test this hypothesis. Three groups of male rats were used: con-trol rats with intraperitoneal injection of placebo (C), 3 days of unloading with placebo injection (3HS), and 3 days of unloading injectedwith CDN1163 (3HSC). Treatment with CDN1163 during 3 days of soleus muscle unloading prevented the upregulation of Ca 2 þ andATP and the slow-to-fast shift in muscle fiber composition. This treatment blocked the decrease in the phosphorylation of the anabolicmarkers [glycogen synthase kinase-3b (GSK3b), eukaryotic translation elongation factor 2 (eEF2), and ribosomal protein S6 (S6,Ser240/244/Ser235/236)], and therefore it is likely that it improved the efficiency of translation in the unloaded muscle, but it did notaffect mTORC1-dependent signaling. Treatment with CDN1163 also modulated the regulation of the Ca2 þ -dependent signaling in mus-cle during unloading via SERCA1 and calsequestrin 2 (CSQ2) and changes in the calcium/calmodulin-dependent protein kinase II(CaMKII) phosphorylation and the content of inositol 1,4,5-trisphosphate receptor (IP3R). In addition, CDN1163 prevented the upregula-tion of the mRNA expression of muscle-specific RING finger protein 1 (MuRF1) [but not ubiquitin ligase muscle atrophy F-box (MAFbx)]and attenuated the increase of casitas B lymphoma-b (Cbl-b) and ubiquitin mRNA expression during unloading. Activation of SERCAwith CDN1163 prevents the upregulation of Ca 2 þ and ATP, as well as calcium-dependent and ubiquitin-proteasome pathwaysmarkers, and improves protein translation efficiency in 3-day unloaded soleus muscle.

Cite: Ksenia Askhatovna Zaripova , Belova S.P. , Sharlo K.A. , Sidorenko D.A. , Kostrominova T.Y. , Shenkman B.S. , Nemirovskaya T.L.
SERCA activation prevents Ca2+ and ATP upregulation during three-day soleus muscle unloading in rats
American Journal of Physiology-regulatory Integrative and Comparative Physiology. 2025. DOI: 10.1152/ajpregu.00177.2024 OpenAlex

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W4410828809

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