FASEB J:Leukotriene B4 和lipoxin A4 能刺激神经干细胞生长和分化
哈佛大学的科学家发现了一种能够刺激大脑内干细胞生长的重要物质。这项研究成果将来可能有助于帕金森病、中风、轴周性硬化性脑炎及大脑白质神经功能障碍患者大脑功能的恢复。研究结果将发表在9月份《美国实验生物学会联合会杂志》FASEB J上，这些物质可能会使病损的神经元恢复功能从而最终修复大脑功能。
研究人员将研究的重点放在两种物质上即LTB4和LXA4，这两种物质在炎症反应和几种细胞的增殖调节中发挥重要作用。LTB4能够使分离自小鼠胚胎大脑的干细胞增殖和分化，并且能够引发其他分化能力有限或缺少分化能力的干细胞分化为神经元。而LXA4能够导致干细胞生长缓慢和凋亡。
《美国实验生物学会联合会杂志》总编辑Gerald Weissmann博士说：“这项研究为广大神经障碍及以前被认为不可治愈的神经损伤患者提供了一种新的治疗方法。”
研究人员还对LTB4对神经干细胞作用的细胞和分子相关机制进行了深入研究。研究结果显示，经过LTB4刺激而产生的细胞具有高水平的LTB4受体，而不是由LTB4刺激而产生的细胞其LTB4受体水平较低。研究人员的研究还进一步表明，LTB4能够上调几种与细胞周期和生长相关的分子，比如细胞周期蛋白和表皮生长因子受体，还能够下调caspase 8等因子，而caspase 8在细胞凋亡中起作用。LXA4的作用与LTB4相反。
原始出处:
Koichiro Wada*,1,2, Makoto Arita,1, Atsushi Nakajima, Kazufumi Katayama*, Chiho Kudo*, Yoshinori Kamisaki* and Charles N. Serhan2,. Leukotriene B4 and lipoxin A4 are regulatory signals for neural stem cell proliferation and differentiation.The FASEB Journal. 2006;20:1785-1792
英文摘要:
Leukotrienes (LTs) and lipoxins (LXs) are lipid mediators that play a key role in regulating acute inflammatory responses. Their roles in neural stem cell (NSC) functions are of interest. We showed here that LTB4 and LXA4 regulated proliferation and differentiation of murine NSCs that were isolated from embryo brains. Proliferation of NSCs was stimulated by LTB4 (3 to 100 nM) and blocked by receptor antagonist (IC50=2.7 µM). In contrast, LXA4, and its aspirin-triggered-15-epi-LXA4 stable analog attenuated growth of NSCs at as little as 1 nM. Both lipoxygenase (LOX) inhibitors and LTB4 receptor antagonists caused apoptosis and cell death. Gene chip analysis revealed that growth-related gene expressions such as epidermal growth factor (EGF) receptor, cyclin E, p27, and caspase 8 were tightly regulated by LTB4; LXA4 gave the opposite gene expressions. In addition to proliferation, LTB4 induced differentiation of NSCs into neurons as monitored by neurite outgrowth and MAP2 expression. These results indicate for the first time that LTB4 and LXA4 directly regulate proliferation and differentiation of NSCs, suggesting these new pathways may be useful in restoring stem cells.—Wada, K., Arita, M., Nakajima, A., Katayama, K., Kudo, C., Kamisaki, Y., Serhan, C. N. Leukotriene B4 and lipoxin A4 are regulatory signals for neural stem cell proliferation and differentiation.
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