TY  - JOUR
AU  - Banjac, Katarina
AU  - Obradović, Milan
AU  - Zafirović, Sonja
AU  - Essack, Magbubah
AU  - Gluvić, Zoran
AU  - Šunderić, Miloš
AU  - Nedić, Olgica
AU  - Isenović, Esma R.
PY  - 2024
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/13184
AB  - 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
T2  - Molecular Biology Reports
T1  - The involvement of Akt, mTOR, and S6K in the in vivo effect of IGF-1 on the regulation of rat cardiac Na+/K+-ATPase
VL  - 51
IS  - 1
DO  - 10.1007/s11033-024-09451-3
ER  - 

@article{
author = "Banjac, Katarina and Obradović, Milan and Zafirović, Sonja and Essack, Magbubah and Gluvić, Zoran and Šunderić, Miloš and Nedić, Olgica and Isenović, Esma R.",
year = "2024",
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",
journal = "Molecular Biology Reports",
title = "The involvement of Akt, mTOR, and S6K in the in vivo effect of IGF-1 on the regulation of rat cardiac Na+/K+-ATPase",
volume = "51",
number = "1",
doi = "10.1007/s11033-024-09451-3"
}

Banjac, K., Obradović, M., Zafirović, S., Essack, M., Gluvić, Z., Šunderić, M., Nedić, O.,& Isenović, E. R.. (2024). The involvement of Akt, mTOR, and S6K in the in vivo effect of IGF-1 on the regulation of rat cardiac Na+/K+-ATPase. in Molecular Biology Reports, 51(1).
https://doi.org/10.1007/s11033-024-09451-3

Banjac K, Obradović M, Zafirović S, Essack M, Gluvić Z, Šunderić M, Nedić O, Isenović ER. The involvement of Akt, mTOR, and S6K in the in vivo effect of IGF-1 on the regulation of rat cardiac Na+/K+-ATPase. in Molecular Biology Reports. 2024;51(1).
doi:10.1007/s11033-024-09451-3 .

Banjac, Katarina, Obradović, Milan, Zafirović, Sonja, Essack, Magbubah, Gluvić, Zoran, Šunderić, Miloš, Nedić, Olgica, Isenović, Esma R., "The involvement of Akt, mTOR, and S6K in the in vivo effect of IGF-1 on the regulation of rat cardiac Na+/K+-ATPase" in Molecular Biology Reports, 51, no. 1 (2024),
https://doi.org/10.1007/s11033-024-09451-3 . .