title: Cyclosporin A inhibits angiotensin II-induced c-Jun NH(2)-terminal kinase activation but not protein synthesis in vascular smooth muscle cells.
abstract: Angiotensin II activates three major mitogen-activated protein kinases (MAPK) in vascular smooth muscle cells. Although other angiotensin II-induced MAPKs activation require transactivation of a growth factor receptor, the detailed mechanism by which angiotensin II activates c-Jun NH(2)-terminal kinase (JNK) remains unclear. Here, an immunosuppressant, cyclosporin A but not FK506, selectively inhibited angiotensin II-induced JNK activation in vascular smooth muscle cells. However, cyclosporin A had no inhibitory effect on angiotensin II-induced protein synthesis. Thus, angiotensin II-induced JNK activation but not protein synthesis is mediated by a mechanism sensitive to cyclosporin A, which is independent from calcineurin in vascular smooth muscle cells.
authors.affiliation: Department of Biochemistry, Vanderbilt University School of Medicine, 658 Light Hall, Nashville, TN 37232, USA.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Saito
authors.forename: Gerald D
authors.initials: GD
authors.lastname: Frank
authors.forename: Evangeline D
authors.initials: ED
authors.lastname: Motley
authors.forename: Hirotoshi
authors.initials: H
authors.lastname: Utsunomiya
authors.forename: Tadashi
authors.initials: T
authors.lastname: Inagami
authors.forename: Satoru
authors.initials: S
authors.lastname: Eguchi
mesh_terms: D000804:Angiotensin II / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D000841:Anisomycin / Q000494:pharmacology; D001013:Aorta, Thoracic; D002478:Cells, Cultured; D016572:Cyclosporine / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D048031:JNK Mitogen-Activated Protein Kinases; D007930:Leucine / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D010766:Phosphorylation; D014176:Protein Biosynthesis; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides / Q000494:pharmacology; D016559:Tacrolimus / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: D004791:Enzyme Inhibitors; D007166:Immunosuppressive Agents; D011500:Protein Synthesis Inhibitors; D013449:Sulfonamides; D000804:Angiotensin II; C017967:W 7; D000841:Anisomycin; D016572:Cyclosporine; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D007930:Leucine; D016559:Tacrolimus