Role of phosphatidylinositol 3-kinase/Akt pathway in angiotensin II and insulin-like growth factor-1 modulation of nitric oxide synthase in vascular smooth muscle cells.
The aim of this study was to examine the role of the phosphatidylinositol 3-kinase (PI3K)/serine/threonine kinase Akt signaling pathway in mediating interactions between angiotensin II (Ang II) and insulin-like growth factor-1 (IGF-1) in regulation of inducible nitric oxide synthase (iNOS) in vascular smooth muscle cells (VSMCs). Exposure to 100 nM IGF-1 for 10 min resulted in increased insulin-receptor substrate-1 associated PI3K activity and Akt kinase activity, whereas 100 nM Ang II pretreatment for 5 min strikingly decreased these IGF-1 effects. NOS activity was also increased in VSMCs following exposure to IGF-1 (10 min up to 24 h). Pretreatment with Ang II for 5 min reduced IGF-1-induced NOS activity. IGF-1 treatment for 24 hr increased iNOS gene transcription, and Ang II pretreatment reduced this stimulation of iNOS gene expression by attenuating PI3K/Akt signaling. These results implicate PI3K/ Akt pathways in Ang II/IGF-1 regulation of iNOS in VSMCs.
Isenovic
Esma R
ER
Department of Biochemistry, SUNY-Health Science Center, Brooklyn, NY 11203, USA.
Meng
Yong
Y
Divald
Andras
A
Milivojevic
Nikola
N
Sowers
James R
JR
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic; D002478:Cells, Cultured; D004347:Drug Interactions; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000201:enzymology*; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D014158:Transcription, Genetic / Q000187:drug effects
D000804:Angiotensin II; D007334:Insulin-Like Growth Factor I; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; C496318:Nos2 protein, rat; C494920:Akt1 protein, rat