title: Adenosine monophosphate-activated protein kinase regulates platelet-derived growth factor-BB-induced vascular smooth muscle cell migration.
abstract: Migration of vascular smooth muscle cells (VSMCs) is essential for repair of vascular injury, development of atherosclerotic lesions and restenosis after angioplasty or by-pass graft surgery. It has been reported that platelet-derived growth factor (PDGF)-BB induces VSMC migration via the p44/p42 mitogen-activated protein (MAP) kinase pathway and the phosphatidylinositol 3 (PI3)-kinase/Akt pathway. Adenosine monophosphate-activated protein kinase (AMPK) is generally known to regulate multiple metabolic pathway. In the present study, we investigated the involvement of AMPK in PDGF-BB-induced migration of VSMCs using, a VSMC line, A10 cells. PDGF-BB induced phosphorylation of AMPK-α at Thr-172 residue. Treatment of A10 cells with compound C, an AMPK inhibitor, suppressed PDGF-BB-induced migration in a concentration-dependent manner (0.01-1μM). Compound C truly attenuated PDGF-BB induced phosphorylation of acetyl-CoA carboxylase, a downstream substance of AMPK. Downregulation of AMPK-α expression by the siRNA appeared an anti-migratory effect on PDGF-BB-induced migration. PDGF-BB-induced phosphorylation of c-Raf, MEK1/2 or p44/p42 MAP kinase, and phosphorylation of PI3-kinase or Akt were markedly suppressed by compound C. In conclusion, our results strongly suggest that PDGF-BB induces activation of AMPK in VSMCs, and subsequently regulates the migration via both the p44/p42 MAP kinase pathway and the PI3-kinase/Akt pathway.
authors.affiliation: Department of Anesthesiology and Pain Medicine, Gifu University Graduate School of Medicine, Yanagido 1-1, Gifu 501-1194, Japan. imiki22@gifu-u.ac.jp
authors.forename: Miki
authors.initials: M
authors.lastname: Iida
authors.forename: Kumiko
authors.initials: K
authors.lastname: Tanabe
authors.forename: Rie
authors.initials: R
authors.lastname: Matsushima-Nishiwaki
authors.forename: Osamu
authors.initials: O
authors.lastname: Kozawa
authors.forename: Hiroki
authors.initials: H
authors.lastname: Iida
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D000818:Animals; D000077214:Becaplermin; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000201:enzymology*; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000201:enzymology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects / Q000502:physiology; D011494:Protein Kinases / Q000378:metabolism*; D019908:Proto-Oncogene Proteins c-raf / Q000378:metabolism; D020574:Proto-Oncogene Proteins c-sis / Q000378:metabolism / Q000494:pharmacology*; D011720:Pyrazoles / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats
chemical_list: D000091162:AMP-Activated Protein Kinase Kinases; D000077214:Becaplermin; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D019869:Phosphatidylinositol 3-Kinases; D011494:Protein Kinases; D019908:Proto-Oncogene Proteins c-raf; D020574:Proto-Oncogene Proteins c-sis; D011720:Pyrazoles; D011743:Pyrimidines; C516138:dorsomorphin