title: Regulation of Akt by arachidonic acid and phosphoinositide 3-kinase in angiotensin II-stimulated vascular smooth muscle cells.
abstract: Angiotensin (Ang) II stimulates cytosolic phospholipase A2(cPLA(2))-dependent release of arachidonic acid (ArAc) in vascular smooth muscle cells (VSMC). ArAc release and production of reactive oxygen species (ROS) lead to the activation of downstream kinases resulting in VSMC growth. To determine the role of Akt in this pathway, we used VSMC to link Ang II-induced ArAc release and ROS production to the activation of Akt and VSMC growth. We observed that Ang II, ArAc, or H(2)O(2) increased Akt activation. The Akt inhibitor SH6 blocked Ang II-, ArAc-, or H(2)O(2)-induced Akt activation, as did inhibition of phosphoinositide 3-kinase (PI(3)K). Inhibition of cPLA(2) blocked Ang II effects, while the ROS scavenger NaC decreased Ang II- and ArAc-induced Akt activation. Inhibition of Akt blocked the (3)H-thymidine incorporation induced by all three agonists. Thus, Ang II-induced ArAc release and ROS production leads to the PI(3)K-dependant activation of Akt and VSMC growth.
authors.affiliation: Kent State University, School of Biomedical Sciences, Cunningham Hall A229, Kent, OH 44242, USA.
authors.forename: Maria L
authors.initials: ML
authors.lastname: Wildroudt
authors.forename: Ernest J
authors.initials: EJ
authors.lastname: Freeman
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic; D016718:Arachidonic Acid / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000201:enzymology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species
chemical_list: D017382:Reactive Oxygen Species; D000804:Angiotensin II; D016718:Arachidonic Acid; D006861:Hydrogen Peroxide; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt