title: Sphingosine-1-phosphate protects intestinal epithelial cells from apoptosis through the Akt signaling pathway.
abstract: OBJECTIVE
  The regulation of apoptosis of intestinal mucosal cells is important in maintenance of normal intestinal physiology.
  
  
  CONCLUSIONS
  Sphingosine-1-phosphate (S1P) has been shown to play a critical role in cellular protection to otherwise lethal stimuli in several nonintestinal tissues.
  
  
  METHODS
  The current study determines whether S1P protected normal intestinal epithelial cells (IECs) from apoptosis and whether Akt activation was the central pathway for this effect.
  
  
  RESULTS
  S1P demonstrated significantly reduced levels of apoptosis induced by tumor necrosis factor-alpha (TNF-alpha)/cycloheximide (CHX). S1P induced increased levels of phosphorylated Akt and increased Akt activity, but did not affect total amounts of Akt. This activation of Akt was associated with decreased levels of both caspase-3 protein levels and of caspase-3 activity. Inactivation of Akt by treatment with the PI3K chemical inhibitor LY294002 or by overexpression of the dominant negative mutant of Akt (DNMAkt) prevented the protective effect of S1P on apoptosis. Additionally, silencing of the S1P-1 receptor by specific siRNA demonstrated a lesser decrease in apoptosis to S1P exposure.
  
  
  CONCLUSIONS
  These results indicate that S1P protects intestinal epithelial cells from apoptosis via an Akt-dependent pathway.
authors.affiliation: Department of Surgery, Cell Biology Group, Baltimore Veterans Affairs Medical Center, University of Maryland School of Medicine, 10 N. Greene Street, Baltimore, MD 21201, USA.
authors.forename: Jose
authors.initials: J
authors.lastname: Greenspon
authors.forename: Ruiyun
authors.initials: R
authors.lastname: Li
authors.forename: Lan
authors.initials: L
authors.lastname: Xiao
authors.forename: Jaladanki N
authors.initials: JN
authors.lastname: Rao
authors.forename: Bernard S
authors.initials: BS
authors.lastname: Marasa
authors.forename: Eric D
authors.initials: ED
authors.lastname: Strauch
authors.forename: Jian-Ying
authors.initials: JY
authors.lastname: Wang
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: Turner
mesh_terms: D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D004789:Enzyme Activation; D004847:Epithelial Cells / Q000502:physiology*; D007413:Intestinal Mucosa / Q000502:physiology*; D008246:Lysophospholipids / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D051381:Rats; D049349:Receptors, Lysosphingolipid / Q000378:metabolism; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000502:physiology; D014162:Transfection
chemical_list: D053148:Caspase 3; D008246:Lysophospholipids; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D049349:Receptors, Lysosphingolipid; D013110:Sphingosine; C060506:sphingosine 1-phosphate