
<oai_dc:dc xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:oai_dc="http://www.openarchives.org/OAI/2.0/oai_dc/">
  <dc:publisher>Springer Link</dc:publisher>
  <dc:format>application/pdf</dc:format>
  <dc:format>67611 bytes</dc:format>
  <dc:subject xml:lang="eng">Heart; IGF-1; Na+/K+-ATPase; S6K; mTOR</dc:subject>
  <dc:source>Molecular Biology Reports</dc:source>
  <dc:source>vol. 51</dc:source>
  <dc:title xml:lang="eng">The involvement of Akt, mTOR, and S6K in the in vivo effect of IGF-1 on the regulation of rat cardiac Na+/K+-ATPase </dc:title>
  <dc:language>eng</dc:language>
  <dc:rights>http://creativecommons.org/licenses/by-nc-nd/4.0/legalcode</dc:rights>
  <dc:description xml:lang="eng">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.</dc:description>
  <dc:date>2024</dc:date>
  <dc:creator>Banjac, Katarina</dc:creator>
  <dc:creator>Obradović, Milan</dc:creator>
  <dc:creator>Zafirović, Sonja</dc:creator>
  <dc:creator>Essack, Magbubah</dc:creator>
  <dc:creator>Gluvić, Zoran</dc:creator>
  <dc:creator id="https://orcid.org/0000-0002-0940-9481">Šunderić, Miloš</dc:creator>
  <dc:creator id="https://orcid.org/0000-0003-2042-0056">Nedić, Olgica</dc:creator>
  <dc:creator>R. Isenovic, Esma</dc:creator>
  <dc:identifier>https://phaidrabg.bg.ac.rs/o:33789</dc:identifier>
  <dc:identifier>doi:10.1007/s11033-024-09451-3 </dc:identifier>
  <dc:type>info:eu-repo/semantics/article</dc:type>
</oai_dc:dc>