title: Sphingosine-1-phosphate inhibits H2O2-induced granulosa cell apoptosis via the PI3K/Akt signaling pathway.
abstract: OBJECTIVE
  To investigate the protective effect of sphingosine-1-phosphate (S1P) against H(2)O(2)-induced apoptosis in human granulosa cell cultures with freshly harvested granulosa cells.
  
  
  METHODS
  Experimental study.
  
  
  METHODS
  Academic medical center for reproductive medicine.
  
  
  METHODS
  Cultures of primary granulosa cells isolated from women undergoing in vitro fertilization (IVF).
  
  
  METHODS
  None.
  
  
  METHODS
  Cell apoptosis and Western blot analysis of signaling pathway proteins.
  
  
  RESULTS
  We found that S1P (1 and 10 mM) statistically significantly decreased granulosa cell apoptosis after H(2)O(2) treatment. The decreased cell apoptosis induced by S1P was abolished after treatment with VPC23019, an inhibitor of S1P1 and S1P3 receptors, W146, an inhibitor of S1P1 receptors, and CAY10444, an inhibitor of S1P3 receptors. A Western blot analysis revealed that the level of phospho-Akt increased and peaked at 10 minutes after 10 mM S1P exposure.
  
  
  CONCLUSIONS
  Treatment with S1P can inhibit the apoptosis of granulosa cells in response to oxidative stress induced by H(2)O(2). The protective effect of S1P is mediated by activating the PI3K/Akt pathway, and the antiapoptotic effect of S1P is mainly mediated through the S1P1 and S1P3 receptor.
authors: Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors: Tatsuo
authors: T
authors: Nakahara
authors: Akira
authors: A
authors: Iwase
authors: Tomoko
authors: T
authors: Nakamura
authors: Mika
authors: M
authors: Kondo
authors: Bayasula
authors: Hiroharu
authors: H
authors: Kobayashi
authors: Sachiko
authors: S
authors: Takikawa
authors: Shuichi
authors: S
authors: Manabe
authors: Maki
authors: M
authors: Goto
authors: Tomomi
authors: T
authors: Kotani
authors: Fumitaka
authors: F
authors: Kikkawa
mesh_terms: D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D019610:Cytoprotection / Q000187:drug effects / Q000502:physiology; D004347:Drug Interactions; D005260:Female; D005307:Fertilization in Vitro; D006107:Granulosa Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D008246:Lysophospholipids / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000502:physiology; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D061251:Primary Cell Culture; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D049349:Receptors, Lysosphingolipid / Q000037:antagonists & inhibitors / Q000378:metabolism; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D008246:Lysophospholipids; D016877:Oxidants; D049349:Receptors, Lysosphingolipid; C060506:sphingosine 1-phosphate; D006861:Hydrogen Peroxide; D019869:Phosphatidylinositol 3-Kinases; C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt; D013110:Sphingosine