title: Growth factor-induced phosphoinositide 3-OH kinase/Akt phosphorylation in smooth muscle cells: induction of cell proliferation and inhibition of cell death.
abstract: OBJECTIVE
  The signaling pathways mediating proliferation and apoptosis in vascular smooth muscle cells (VSMC) are not well established. It has previously been shown that activation of the phosphoinositide 3-OH kinase (PI3K)/Akt pathway or the ERK 1/2 pathway can mediate anti-apoptotic function in different cell types. This study determined the specific contribution of the PI3K/Akt and ERK pathway in the regulation of apoptosis and proliferation of VSMC.
  
  
  RESULTS
  Incubation of rat VSMC with FCS, insulin or IGF-1 time-dependently stimulated the phosphorylation of Akt, however FCS but not insulin or IGF-1 activated the MAP-kinase ERK 1/2. Moreover, insulin inhibited H(2)O(2)-induced apoptosis via the Akt pathway as demonstrated by pharmacological inhibition of the PI3K or overexpression of a dominant negative Akt mutant. In contrast, FCS inhibited H(2)O(2)-induced apoptosis via the Akt and also the ERK pathway. FCS, but not insulin or IGF-1 induced VSMC proliferation, suggesting that Akt activation is necessary but not sufficient for VSMC proliferation. FCS-induced proliferation of VSMC was only mediated via the Akt pathway and not the ERK pathway.
  
  
  CONCLUSIONS
  These results define a link between cell proliferation and programmed cell death in VSMC via the same signal transduction pathway, namely activation of the serine/threonine kinase Akt, which may have significant implication for the development of vascular diseases or remodeling.
authors.affiliation: Molecular Cardiology, Department of Internal Medicine IV, University of Frankfurt, Frankfurt, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Jung
authors.forename: J
authors.initials: J
authors.lastname: Haendeler
authors.forename: C
authors.initials: C
authors.lastname: Goebel
authors.forename: A M
authors.initials: AM
authors.lastname: Zeiher
authors.forename: S
authors.initials: S
authors.lastname: Dimmeler
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001011:Aorta; D017209:Apoptosis / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D005434:Flow Cytometry; D006133:Growth Substances / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*; D013268:Stimulation, Chemical
chemical_list: D006133:Growth Substances; D007328:Insulin; D007334:Insulin-Like Growth Factor I; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; C494920:Akt1 protein, rat