{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T03:08:03Z","timestamp":1784689683120,"version":"3.55.0"},"reference-count":69,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,1,6]],"date-time":"2025-01-06T00:00:00Z","timestamp":1736121600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["24-15-00088"],"award-info":[{"award-number":["24-15-00088"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>During skeletal muscle unloading, phosphoinositide 3-kinase (PI3K), and especially PI3K gamma (PI3K\u03b3), can be activated by changes in membrane potential. Activated IP3 can increase the ability of Ca2+ to enter the nucleus through IP3 receptors. This may contribute to the activation of transcription factors that initiate muscle atrophy processes. LY294002 inhibitor was used to study the role of PI3K in the ATP-dependent regulation of skeletal muscle signaling during three days of unloading. Inhibition of PI3K during soleus muscle unloading slows down the atrophic processes and prevents the accumulation of ATP and the expression of the E3 ubiquitin ligase MuRF1 and ubiquitin. It also prevents the increase in the expression of IP3 receptors and regulates the activity of Ca2+-dependent signaling pathways by reducing the mRNA expression of the Ca2+-dependent marker calcineurin (CaN) and decreasing the phosphorylation of CaMKII. It also affects the regulation of markers of anabolic signaling in unloaded muscles: IRS1 and 4E-BP. PI3K is an important mediator of skeletal muscle atrophy during unloading. Developing strategies for the localized skeletal muscle release of PI3K inhibitors might be one of the future treatments for inactivity and disease-induced muscle atrophy.<\/jats:p>","DOI":"10.3390\/ijms26010414","type":"journal-article","created":{"date-parts":[[2025,1,6]],"date-time":"2025-01-06T09:17:02Z","timestamp":1736155022000},"page":"414","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Role of PI3 Kinases in Cell Signaling and Soleus Muscle Atrophy During Three Days of Unloading"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6537-3524","authenticated-orcid":false,"given":"Ksenia A.","family":"Zaripova","sequence":"first","affiliation":[{"name":"Myology Laboratory, Institute of Biomedical Problems (IBP), RAS, 123007 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svetlana P.","family":"Belova","sequence":"additional","affiliation":[{"name":"Myology Laboratory, Institute of Biomedical Problems (IBP), RAS, 123007 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5863-7114","authenticated-orcid":false,"given":"Tatiana Y.","family":"Kostrominova","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Cell Biology and Physiology, Indiana University School of Medicine-Northwest, Gary, IN 46202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boris S.","family":"Shenkman","sequence":"additional","affiliation":[{"name":"Myology Laboratory, Institute of Biomedical Problems (IBP), RAS, 123007 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1624-4750","authenticated-orcid":false,"given":"Tatiana L.","family":"Nemirovskaya","sequence":"additional","affiliation":[{"name":"Myology Laboratory, Institute of Biomedical Problems (IBP), RAS, 123007 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,6]]},"reference":[{"key":"ref_1","first-page":"1299","article-title":"Regulation of Protein Synthesis in Inactivated Skeletal Muscle: Signal Inputs, Protein Kinase Cascades, and Ribosome Biogenesis","volume":"83","author":"Mirzoev","year":"2018","journal-title":"Biochemistry"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1152\/jappl.1999.87.1.386","article-title":"Intracellular Ca2+ transients in mouse soleus muscle after hindlimb unloading and reloading","volume":"87","author":"Ingalls","year":"1999","journal-title":"J. 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