Inhibitors of p38 mitogen-activated protein kinase enhance proliferation of mouse neural stem cells
Inhibitors of p38 mitogen-activated protein kinase enhance proliferation of mouse neural stem cells
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DOI：
10.1002/jnr.21668
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发表时间：
2008-08-01
影响因子：
4.2
通讯作者：
Takamatsu, Ken
中科院分区：
文献类型：
--
作者：
Sato, Kenichiro;Hamanoue, Makoto;Takamatsu, Ken
p38丝裂原活化蛋白激酶（MAPK）在环境胁迫下被诱导。尽管p38 MAPK参与了多种细胞过程，包括中枢神经系统（CNS）中的细胞增殖、分化和分化细胞的存活，但p38 MAPK在发育中的脑中的表达谱和作用仍在很大程度上未知。在本研究中，我们证明，p38 MAPK主要表达在巢蛋白阳性细胞在胚胎第10天（E10）的大脑皮层和蛋白质的表达逐渐下降，在发展过程中。为了研究p38 MAPK在胚胎脑中的作用，将两种选择性p38 MAPK抑制剂SB 202190和SB 203580添加到来自E10-E14脑的原代神经元培养物中。暴露于这些抑制剂7天后，但不暴露于SB 203580的阴性类似物SB 202474，存在许多大的神经球。MAPK抑制剂也选择性地增加从次级神经球纯化的神经干细胞（NSC）的生长速率和溴脱氧尿苷阳性NSC的数量。因此，ID 38 MAPK抑制剂是NSC增殖的有效刺激剂，并且p38 MAPK可能是早期脑发育期间NSC增殖的内在负调节剂。(c)2008 Wiley-Liss，Inc.
The p38 mitogen-activated protein kinase (MAPK) is induced in response to environmental stress. Although p38 MAPK has been implicated in diverse cellular processes, including cell proliferation, differentiation, and survival of differentiated cells in the central nervous system (CNS), the expression profile and roles of p38 MAPK in the developing brain remain largely unknown. In the present study, we demonstrate that p38 MAPK is expressed predominantly in nestin-positive cells in the cerebral cortex in embryonic day 10 (E10) brain and that expression of the protein decreases gradually during development. To investigate the roles of p38 MAPK in the embryonic brain, two selective p38 MAPK inhibitors, SB202190 and SB203580, were added to the primary neuronal cultures from E10-E14 brains. After 7 days of exposure to these inhibitors, but not SB202474, a negative analog of SB203580, numerous large neurospheres were present. MAPK inhibitors also selectively increased the growth rate of neural stem cells (NSCs) purified from secondary neurospheres and the number of bromodeoxyuridine-positive NSCs. Thus, ID38 MAPK inhibitors are potent stimulators of NSC proliferation, and p38 MAPK may be an intrinsic negative regulator of NSC proliferation during early brain development. (c) 2008 Wiley-Liss, Inc.