o:33789 The involvement of Akt, mTOR, and S6K in the in vivo effect of IGF-1 on the regulation of rat cardiac Na+/K+-ATPase Učešće Akt, mTOR i S6K u in vivo uticaju IGF-I na regulaciju srčane NA+/K+ ATPaze pacova en ABSTRACT Background We previously demonstrated that insulin-like growth factor-1 (IGF-1) regulates sodium/potassium adenosine triphosphatase (Na+/K+-ATPase) in vascular smooth muscle cells (VSMC) via phosphatidylinositol-3 kinase (PI3K). Taking into account that others’ work show that IGF-1 activates the PI3K/protein kinase B (Akt) signaling pathway in many different cells, we here further questioned if the Akt/mammalian target of rapamycin (mTOR)/ribosomal protein p70 S6 kinase (S6K) pathway stimulates Na+/K+-ATPase, an essential protein for maintaining normal heart function. Methods and results There were 14 adult male Wistar rats, half of whom received bolus injections of IGF-1 (50 μg/kg) for 24 h. We evaluated cardiac Na+/K+-ATPase expression, activity, and serum IGF-1 levels. Additionally, we examined the phosphorylated forms of the following proteins: insulin receptor substrate (IRS), phosphoinositide-dependent kinase-1 (PDK-1), Akt, mTOR, S6K, and α subunit of Na+/K+-ATPase. Additionally, the mRNA expression of the Na+/K+-ATPase α1 subunit was evaluated. Treatment with IGF-1 increases levels of serum IGF-1 and stimulates Na+/K+-ATPase activity, phosphorylation of α subunit of Na+/K+-ATPase on Ser23, and protein expression of α2 subunit. Furthermore, IGF-1 treatment increased phosphorylation of IRS-1 on Tyr1222, Akt on Ser473, PDK-1 on Ser241, mTOR on Ser2481 and Ser2448, and S6K on Thr421/Ser424. The concentration of IGF-1 in serum positively correlates with Na+/K+-ATPase activity and the phosphorylated form of mTOR (Ser2448), while Na+/K+-ATPase activity positively correlates with the phosphorylated form of IRS-1 (Tyr1222) and mTOR (Ser2448). Conclusion These results indicate that the Akt/mTOR/S6K signalling pathway may be involved in the IGF-1 regulating cardiac Na+/K+-ATPase expression and activity. Heart; IGF-1; Na+/K+-ATPase; S6K; mTOR 1552099 10.1007/s11033-024-09451-3 2024-05-24T11:24:29.924Z 44 yes 46 Katarina Banjac Department of Radiobiology and Molecular Genetics, "VINČA" Institute of Nuclear Sciences-National Institute of the Republic of Serbia, University of Belgrade, Serbia Milan Obradović Department of Radiobiology and Molecular Genetics, "VINČA" Institute of Nuclear Sciences-National Institute of the Republic of Serbia, University of Belgrade, Serbia person Sonja Zafirović Department of Radiobiology and Molecular Genetics, "VINČA" Institute of Nuclear Sciences-National Institute of the Republic of Serbia, University of Belgrade, Serbia person Magbubah Essack Computational Bioscience Research Center (CBRC), King Abdullah University of Science and Technology (KAUST), Thuwal, Kingdom of Saudi Arabia person Zoran Gluvić Clinic of Internal Medicine, School of Medicine, University Clinical-Hospital Centre Zemun-Belgrade, University of Belgrade, Serbia person Miloš Šunderić University of Belgrade, Institute for the Application of Nuclear Energy INEP, Serbia doktor biohemijskih nauka person 0000-0002-0940-9481 Olgica Nedić University of Belgrade, Institute for the Application of Nuclear Energy INEP, Serbia doktor biohemijskih nauka person 0000-0003-2042-0056 Esma R. Isenovic Department of Radiobiology and Molecular Genetics, "VINČA" Institute of Nuclear Sciences-National Institute of the Republic of Serbia, University of Belgrade, Serbia person application/pdf 67611 https://phaidrabg.bg.ac.rs/o:33789 no yes 18 70 92000001 11A28 11A2810 11A29 11A2905 Molecular Biology Reports 51 Springer Link 2024