title: Sphingosine-1-phosphate activates the AKT pathway to inhibit chemotherapy induced human granulosa cell apoptosis.
abstract: To investigate whether sphingosine-1-phosphate (S1P), an apoptosis-inhibitor would be able to inhibit chemotherapy induced human granulosa cell apoptosis. Cultures of primary granulosa cells were isolated from women undergoing in vitro fertilization (IVF). MTT assay was used to measure the optimum concentration of CTX and S1P acts on human granulosa cells. Granulosa cells were added with pertussis toxin (PTX), the PI3K inhibitor LY294002. Western blot analysis was used to analyze the signaling pathway of proteins and cell apoptosis. We found that S1P (10 mm) statistically significantly decreased granulosa cell apoptosis after cyclophosphamide (CTX) treatment. The decreased cell apoptosis induced by S1P was abolished after treatment with LY294002, PI3K inhibitor.
  
  
  CONCLUSIONS
  Treatment with S1P can inhibit the CTX-induced granulosa cell apoptosis. The S1P protective effect is mediated by activating the PI3K/Akt pathway.
authors.affiliation: a Department of Reproductive Medicine , Xiangya Hospital, Central South University , Changsha , P.R. China and.
authors.forename: Shuyi
authors.initials: S
authors.lastname: Li
authors.affiliation: b Department of Obstetrics and Gynaecology , The Second Xiangya Hospital, Central South University , Changsha , P.R. China.
authors.forename: Jianling
authors.initials: J
authors.lastname: Chen
authors.affiliation: b Department of Obstetrics and Gynaecology , The Second Xiangya Hospital, Central South University , Changsha , P.R. China.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Fang
authors.affiliation: b Department of Obstetrics and Gynaecology , The Second Xiangya Hospital, Central South University , Changsha , P.R. China.
authors.forename: Xiaomeng
authors.initials: X
authors.lastname: Xia
mesh_terms: D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects*; D017209:Apoptosis / Q000187:drug effects; D002478:Cells, Cultured; D003520:Cyclophosphamide / Q000009:adverse effects*; D004353:Drug Evaluation, Preclinical; D005260:Female; D006107:Granulosa Cells / Q000187:drug effects*; D006801:Humans; D008246:Lysophospholipids / Q000494:pharmacology / Q000627:therapeutic use*; D010766:Phosphorylation / Q000187:drug effects; D016649:Primary Ovarian Insufficiency / Q000139:chemically induced / Q000517:prevention & control*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D018906:Antineoplastic Agents, Alkylating; D008246:Lysophospholipids; C060506:sphingosine 1-phosphate; D003520:Cyclophosphamide; D051057:Proto-Oncogene Proteins c-akt; D013110:Sphingosine
keywords: Apoptosis; S1P; granulosa cell; ovarian function; sphingosine-1-phosphate