Eicosapentaenoic acid attenuates dexamethasome-induced apoptosis by inducing adaptive autophagy via GPR120 in murine bone marrow-derived mesenchymal stem cells.
Eicosapentaenoic acid attenuates dexamethasome-induced apoptosis by inducing adaptive autophagy via GPR120 in murine bone marrow-derived mesenchymal stem cells.
复制标题
二十碳五烯酸通过 GPR120 诱导小鼠骨髓间充质干细胞适应性自噬，从而减弱地塞米松诱导的细胞凋亡
DOI：
10.1038/cddis.2016.144
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发表时间：
2016-05-26
影响因子：
9
通讯作者：
Luo ZJ
中科院分区：
文献类型：
--
作者：
Gao B;Han YH;Wang L;Lin YJ;Sun Z;Lu WG;Hu YQ;Li JQ;Lin XS;Liu BH;Jie Q;Yang L;Luo ZJ
糖皮质激素的长期使用是临床上普遍存在的问题，目前除了停止使用外没有有效的解决办法。二十碳五烯酸（EPA）是一种ω-3长链多不饱和脂肪酸（n-3 PUFA），主要存在于鱼或鱼油中，据报道可促进细胞活力和改善骨代谢。然而，很少有人知道EPA对地塞米松（Dex）诱导的细胞凋亡的影响。在这项研究中，我们发现EPA诱导小鼠骨髓间充质干细胞（mBMMSCs）的自噬。同时，EPA，而不是花生四烯酸（AA），显着抑制右旋糖酐诱导的细胞凋亡和促进mBMMSCs的活力。我们还观察到EPA诱导的自噬受GPR 120调节，但不受GPR 40调节。进一步的实验表明，EPA诱导的自噬机制与GPR 120的调节有关，涉及AMP活化蛋白激酶活性形式的增加和哺乳动物RAPA靶标活性的降低。体内实验支持EPA通过GPR 120介导的适应性自噬诱导对Dex诱导的细胞凋亡的保护作用。总之，我们的研究结果可能有重要的意义，在制定未来的战略，使用EPA在预防和治疗的副作用引起的长期右旋糖酐滥用。
Long-term use of glucocorticoids is a widespread clinical problem, which currently has no effective solution other than discontinuing the use. Eicosapentaenoic acid (EPA), an omega-3 long chain polyunsaturated fatty acid (n-3 PUFA), which is largely contained in fish or fish oil, has been reported to promote cell viability and improve bone metabolism. However, little is known about the effects of EPA on dexamethasome (Dex)-induced cell apoptosis. In this study, we showed that EPA-induced autophagy of murine bone marrow-derived mesenchymal stem cells (mBMMSCs). Meanwhile, EPA, but not arachidonic acid (AA), markedly inhibited Dex-induced apoptosis and promoted the viability of mBMMSCs. We also observed that EPA-induced autophagy was modulated by GPR120, but not GPR40. Further experiments showed that the mechanism of EPA-induced autophagy associated with GPR120 modulation involved an increase in the active form of AMP-activated protein kinase and a decrease in the activity of mammalian target of RAPA. The protective effect of EPA on Dex-induced apoptosis via GPR120-meditated induction of adaptive autophagy was supported by in vivo experiments. In summary, our findings may have important implications in developing future strategies to use EPA in the prevention and therapy of the side effects induced by long-term Dex-abuse.