title: Involvement of phosphatidylinositol 3-kinase and mitogen-activated protein kinase pathways in AII-mediated enhanced expression of Gi proteins in vascular smooth muscle cells.
abstract: We have previously demonstrated that angiotensin II increased Gialpha-2 and Gialpha-3 expression at both protein and mRNA levels in vascular smooth muscle cell (VSMC). The present study was undertaken to investigate the mechanisms responsible for AII-induced enhanced expression of Gi proteins. The levels of Gi protein were determinated by immunoblotting techniques using specific antibodies against Gialpha-2 and Gialpha-3. AII treatment of VSMC increased the levels of Gialpha-2 and Gialpha-3 proteins and actinomycin D, an inhibitor of RNA synthesis attenuated the AII-evoked enhanced expression of Gialpha-2 and Gialpha-3 proteins. In addition, wortmannin, an inhibitor of phosphatidylinositol 3-kinase (PI-3-K), rapamycin, an inhibitor of p70(S6K) and PD 098059, an inhibitor of mitogen-activated protein kinase (MAPK) kinase were able to inhibit AII-induced enhanced expression of Gialpha-2 and Gialpha-3 to various degrees. The attenuation of AII-evoked enhanced levels of Gialpha-2 and Gialpha-3 by PD 098059 was concentration dependent. At 50 microM, PD 098059 was able to completely attenuate the enhanced levels of Gialpha-2 and Gialpha-3 caused by AII treatment. These data suggest that the enhanced expression of Gi-proteins by AII treatment may be attributed to increased RNA synthesis of Gi-proteins, and MAPK kinase, PI-3-Kinase and p70(S6K) may be involved in AII-mediated increased expression of Gi-proteins in VSMC.
authors.affiliation: Department of Physiology, Faculty of Medicine, Université de Montréal, C.P. 6128, Succ. Centre-ville, Québec, Montréal, Canada.
authors.forename: C
authors.initials: C
authors.lastname: Ge
authors.forename: M B
authors.initials: MB
authors.lastname: Anand-Srivastava
mesh_terms: D000730:Androstadienes / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002478:Cells, Cultured; D003609:Dactinomycin / Q000494:pharmacology; D004622:Embryo, Mammalian; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005419:Flavonoids / Q000494:pharmacology; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000096:biosynthesis / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D019893:Ribosomal Protein S6 Kinases / Q000378:metabolism; D020123:Sirolimus / Q000494:pharmacology; D014158:Transcription, Genetic; D000077191:Wortmannin
chemical_list: D000730:Androstadienes; D004791:Enzyme Inhibitors; D005419:Flavonoids; D012333:RNA, Messenger; D000804:Angiotensin II; D003609:Dactinomycin; D019869:Phosphatidylinositol 3-Kinases; D019893:Ribosomal Protein S6 Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; D020123:Sirolimus; D000077191:Wortmannin