title: Ang II attenuates IGF-1-stimulated Na+, K(+)-ATPase activity via PI3K/Akt pathway in vascular smooth muscle cells.
abstract: We have investigated the role of phosphatidylinositol 3-kinase (PI3K) and serine/threonine protein kinase B (Akt) in mediating vascular smooth muscle cells (VSMC) sodium pump (Na+, K(+)-ATPase) regulatory interactions between insulin-like growth factor-1 (IGF-1) and angiotensin II (Ang II). Treatment with IGF-1 (100 nM) for 30 min or Ang II (100 nM) for 10 min increased sodium pump activity. Pretreatment with Ang II for 10 min, abolished IGF-1 increased sodium pump activity. Given separately for 6 h, Ang II and IGF-1 stimulated alpha1 mRNA accumulation. Phosphorylation on Ser473 of Akt was increased after treatment with both IGF-1 and Ang II. Pretreatment with 100 nM of PI3K inhibitor Wortmannin (WT) for 30 min decreased: IGF-1 and Ang II-stimulated pump activity, phosphorylation of Akt and PI3K protein expression. Pretreatment with Ang II attenuated IGF-1-stimulated sodium pump activity, phosphorylation of Akt and PI3K protein expression. IGF-1 increased the association between IRS-1 and p85, and Ang II as well as PI3K inhibition decreased this IGF-1 effect. These results suggest that Ang II, which increases pump activity alone, reduces the IGF-1 stimulation of sodium pump activity by attenuating PI3K/Akt signaling. These results implicate PI3K/Akt pathways in Ang II/IGF-1 regulation of the sodium pump in VSMC.
authors.affiliation: Departments of Cell Biology, Biochemistry and Medicine, SUNY-Health Science Center and VA Medical Center, Brooklyn, NY 11203, USA.
authors.forename: Esma R
authors.initials: ER
authors.lastname: Isenovic
authors.forename: Yong
authors.initials: Y
authors.lastname: Meng
authors.forename: Nasir
authors.initials: N
authors.lastname: Jamali
authors.forename: Nikola
authors.initials: N
authors.lastname: Milivojevic
authors.forename: James R
authors.initials: JR
authors.lastname: Sowers
mesh_terms: D000730:Androstadienes / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D000077191:Wortmannin
chemical_list: D000730:Androstadienes; D000804:Angiotensin II; D004791:Enzyme Inhibitors; D007334:Insulin-Like Growth Factor I; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D000254:Sodium-Potassium-Exchanging ATPase; D000077191:Wortmannin; C494920:Akt1 protein, rat