title: Phosphatidylinositol 3-kinase/Akt plays a role in sphingosine 1-phosphate-stimulated HSP27 induction in osteoblasts.
abstract: We previously reported that p38 mitogen-activated protein (MAP) kinase plays a part in sphingosine 1-phosphate-stimulated heat shock protein 27 (HSP27) induction in osteoblast-like MC3T3-E1 cells. In the present study, we investigated whether phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) is involved in the induction of HSP27 in these cells. Sphingosine 1-phosphate time dependently induced the phosphorylation of Akt. Akt inhibitor, 1L-6-hydroxymethyl-chiro-inositol 2-(R)-2-O-methyl-3-O-octadecylcarbonate, reduced the HSP27 induction stimulated by sphingosine 1-phosphate. The sphingosine 1-phosphate-induced phosphorylation of GSK-3beta was suppressed by Akt inhibitor. The sphingosine 1-phosphate-induced HSP27 levels were attenuated by LY294002 or wortmannin, PI3K inhibitors. Furthermore, LY294002 or Akt inhibitor did not affect the sphingosine 1-phosphate-induced phosphorylation of p38 MAP kinase and SB203580, a p38 MAP kinase inhibitor, had little effect on the phosphorylation of Akt. These results suggest that PI3K/Akt plays a part in the sphingosine 1-phosphate-stimulated induction of HSP27, maybe independently of p38 MAP kinase, in osteoblasts.
authors.affiliation: Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Takai
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Tokuda
authors.forename: Rie
authors.initials: R
authors.lastname: Matsushima-Nishiwaki
authors.forename: Yoshiteru
authors.initials: Y
authors.lastname: Hanai
authors.forename: Kanefusa
authors.initials: K
authors.lastname: Kato
authors.forename: Osamu
authors.initials: O
authors.lastname: Kozawa
mesh_terms: D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D002867:Chromones / Q000494:pharmacology; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006360:Heat-Shock Proteins / Q000378:metabolism*; D008246:Lysophospholipids / Q000494:pharmacology*; D051379:Mice; D009025:Morpholines / Q000494:pharmacology; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D013997:Time Factors; D000077191:Wortmannin
chemical_list: D000730:Androstadienes; D002867:Chromones; D006360:Heat-Shock Proteins; D008246:Lysophospholipids; D009025:Morpholines; D047428:Protein Kinase Inhibitors; C060506:sphingosine 1-phosphate; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D019869:Phosphatidylinositol 3-Kinases; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3; D013110:Sphingosine; D000077191:Wortmannin