Details

Autor(en) / Beteiligte

• Banjac, Katarina
• Obradovic, Milan
• Zafirovic, Sonja
• Essack, Magbubah
• Gluvic, Zoran
• Sunderic, Milos
• Nedic, Olgica
• Isenovic, Esma R.

Titel

The involvement of Akt, mTOR, and S6K in the in vivo effect of IGF-1 on the regulation of rat cardiac Na+/K+-ATPase

Ist Teil von

• Molecular biology reports, 2024-12, Vol.51 (1), p.517-517, Article 517

Ort / Verlag

Dordrecht: Springer Netherlands

Erscheinungsjahr

2024

Quelle

SpringerLink

Beschreibungen/Notizen

• 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 α 1 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 Ser 23 , and protein expression of α 2 subunit. Furthermore, IGF-1 treatment increased phosphorylation of IRS-1 on Tyr 1222 , Akt on Ser 473 , PDK-1 on Ser 241 , mTOR on Ser 2481 and Ser 2448 , and S6K on Thr 421 /Ser 424 . The concentration of IGF-1 in serum positively correlates with Na + /K + -ATPase activity and the phosphorylated form of mTOR (Ser 2448 ), while Na + /K + -ATPase activity positively correlates with the phosphorylated form of IRS-1 (Tyr 1222 ) and mTOR (Ser 2448 ). 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.