Latanoprost Promotes Neurite Outgrowth in Differentiated RGC-5 Cells via the PI3K-Akt-mTOR Signaling Pathway
Latanoprost Promotes Neurite Outgrowth in Differentiated RGC-5 Cells via the PI3K-Akt-mTOR Signaling Pathway
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DOI：
10.1007/s10571-011-9653-x
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发表时间：
2011-01
影响因子：
4
通讯作者：
Jun Zheng;Xue-mei Feng;Lina Hou;Yong-yao Cui;Liang Zhu;Jian Ma;Z. Xia;W. Zhou;Hongzhuan Chen
中科院分区：
文献类型：
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作者：
Jun Zheng;Xue-mei Feng;Lina Hou;Yong-yao Cui;Liang Zhu;Jian Ma;Z. Xia;W. Zhou;Hongzhuan Chen
拉坦前列素是天然前列腺素 F2a (PGF2a) 的合成衍生物，是一种强效抗青光眼药物，具有降眼压和神经保护作用。然而，拉坦前列素对视网膜神经节细胞（RGC）的神经再生作用和信号通路仍不清楚。本研究的目的是探讨拉坦前列素对分化的RGC-5细胞的再生作用及其潜在机制。通过 Cell Counting Kit-8 (CCK-8) 测定法测定细胞活力，并通过 ArrayScan HCS Reader 和 Neurite outgrowth BioApplication 检查神经突长度。通过蛋白质印迹分析研究 Akt 磷酸化 (p-Akt) 和哺乳动物雷帕霉素磷酸化靶点 (p-mTOR) 的表达。结果表明，与对照相比，0.1 μM 拉坦前列素（临床治疗浓度）显着提高了细胞活力。同时，0.1 μM 拉坦前列素与睫状神经营养因子（CNTF）类似，可明显促进神经突生长，同时增加 p-Akt 和 p-mTOR 表达水平。拉坦前列素的作用可被前列腺素 F 受体 (FP 受体) 抑制剂 AL8810、磷酸肌醇 3-激酶 (PI3K) 抑制剂 LY294002 和 mTOR 抑制剂雷帕霉素阻断。这项研究提供了新的体外证据，表明拉坦前列素可以通过 FP 受体介导的 PI3K-Akt-mTOR 信号通路调节来促进神经突生长。这一发现可能有助于更好地理解拉坦前列素治疗青光眼的新机制以及前列腺素的生理调节活性。
Latanoprost, a synthetic derivative of the natural prostaglandin F2a(PGF2a), is a powerful antiglaucoma agent with ocular hypotensive and neuroprotective effects. However, the neuroregenerative effect and signaling pathway of latanoprost in retinal ganglion cells (RGCs) are still unknown. The purpose of this study is to investigate the regenerative effect of latanoprost in differentiated RGC-5 cells and its underlying mechanisms. Cell viability was determined by Cell Counting Kit-8 (CCK-8) assay and neurite length was examined by ArrayScan HCS Reader and Neurite outgrowth BioApplication. Expressions of Akt phosphorylation (p-Akt) and mammalian target of rapamycin phosphorylation (p-mTOR) were investigated by Western blot analysis. The results indicated that 0.1 μM latanoprost (at a clinically therapeutic concentration) significantly increased cell viability as compared with control. Meanwhile, 0.1 μM latanoprost resulted in the obvious promotion of neurite outgrowth similar to ciliary neurotrophic factor (CNTF) and simultaneously increased the levels of p-Akt and p-mTOR expression. The effects of latanoprost were blocked by the Prostaglandin F receptor (FP receptor) inhibitor AL8810, the phosphoinositide 3-kinase (PI3K) inhibitor LY294002 and the mTOR inhibitor rapamycin. This study presents novel in vitro evidence that latanoprost could promote neurite outgrowth through an FP receptor-mediated modulation of the PI3K-Akt-mTOR signaling pathway. This finding may provide insight into a better understanding of a new mechanism of latanoprost for glaucoma therapy and into the physiological-modulating activities of prostaglandins.