Sphingosine-1-phosphate inhibits H2O2-induced granulosa cell apoptosis via the PI3K/Akt signaling pathway
Sphingosine-1-phosphate inhibits H2O2-induced granulosa cell apoptosis via the PI3K/Akt signaling pathway
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DOI：
10.1016/j.fertnstert.2012.06.008
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发表时间：
2012-10-01
影响因子：
6.7
通讯作者：
Kikkawa, Fumitaka
中科院分区：
文献类型：
--
作者：
Nakahara, Tatsuo;Iwase, Akira;Kikkawa, Fumitaka
目的：研究鞘氨醇-1-磷酸（S1 P）对H2 O2诱导的人颗粒细胞凋亡的保护作用。设计：实验研究。设置：生殖医学学术医学中心。患者：从接受体外受精（IVF）的妇女中分离的原代颗粒细胞培养物。干预：无。主要结果测量：细胞凋亡和信号通路蛋白的Western印迹分析结果：我们发现S1 P（1和10 mM）在统计学上显著降低H2 O2处理后的颗粒细胞凋亡。经S1 P1和S1 P3受体抑制剂VPC 23019、S1 P1受体抑制剂W146和S1 P3受体抑制剂CAY 10444处理后，S1 P诱导的细胞凋亡减少被消除。Western blot分析显示，10 mM S1 P处理后颗粒细胞磷酸化Akt水平升高，并在10 min达到峰值。结论：S1 P处理可抑制H2 O2诱导的颗粒细胞凋亡。S1 P的保护作用是通过激活PI 3 K/Akt途径介导的，而S1 P的抗凋亡作用主要通过S1 P1和S1 P3受体介导。（Fertil Steril（R）2012;98：1001-8.（C）2012年由美国生殖医学协会。
Objective: To investigate the protective effect of sphingosine-1-phosphate (S1P) against H2O2-induced apoptosis in human granulosa cell cultures with freshly harvested granulosa cells.Design: Experimental study.Setting: Academic medical center for reproductive medicine.Patient(s): Cultures of primary granulosa cells isolated from women undergoing in vitro fertilization (IVF).Intervention(s): None.Main Outcome Measure(s): Cell apoptosis and Western blot analysis of signaling pathway proteins.Result(s): We found that S1P (1 and 10 mM) statistically significantly decreased granulosa cell apoptosis after H2O2 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.Conclusion(s): Treatment with S1P can inhibit the apoptosis of granulosa cells in response to oxidative stress induced by H2O2. 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. (Fertil Steril (R) 2012;98:1001-8. (C)2012 by American Society for Reproductive Medicine.)