ETOH inhibits embryonic neural stem/precursor cell proliferation via PLD signaling
ETOH inhibits embryonic neural stem/precursor cell proliferation via PLD signaling
复制标题
DOI：
10.1016/j.bbrc.2008.03.060
复制
发表时间：
2008-05-23
影响因子：
3.1
通讯作者：
Tanoue, Akito
中科院分区：
文献类型：
--
作者：
Fujita, Yuko;Hiroyama, Masami;Tanoue, Akito
虽然母亲在怀孕期间过量饮酒已知对胎儿神经发育有不良影响，但对这些影响的潜在机制知之甚少。为了研究这些机制，我们研究了乙醇（ETOH）对神经干/前体细胞（NSC）增殖的毒性作用。在神经干细胞培养中，磷脂酶D（PLD）在表皮生长因子（EGF）和成纤维细胞生长因子2（FGF 2）刺激后被激活。神经干细胞暴露于ETOH抑制细胞增殖，而它对细胞死亡没有影响。磷脂酸（Phosphatidic acid，PA）是PLD产生的信号信使，可逆转ETCH对NSC增殖的抑制作用。用异丁醇阻断PLD信号可抑制细胞增殖。ETOH诱导的NSC增殖抑制和PA对ETOH诱导的抑制的保护作用是通过细胞外信号调节激酶信号传导介导的。这些结果表明暴露于ETOH通过改变PLD信号通路损害NSC增殖。(c)2008年爱思唯尔公司All rights reserved.
While a mother's excessive alcohol consumption during pregnancy is known to have adverse effects on fetal neural development, little is known about the underlying mechanism of these effects. In order to investigate these mechanisms, we investigated the toxic effect of ethanol (ETOH) on neural stem/precursor cell (NSC) proliferation. In cultures of NSCs, phospholipase D (PLD) is activated following stimulation with epidermal growth factor (EGF) and fibroblast growth factor 2 (FGF2). Exposure of NSCs to ETOH suppresses cell proliferation, while it has no effect on cell death. Phosphatidic acid (PA), which is a signaling messenger produced by PLD, reverses ETCH inhibition of NSC proliferation. Blocking the PLD signal by I butanol suppresses the proliferation. ETOH-induced suppression of NSC proliferation and the protective effect of PA for ETOH-induced suppression are mediated through extracellular signal-regulated kinase signaling. These results indicate that exposure to ETOH impairs NSC proliferation by altering the PLD signaling pathway. (c) 2008 Elsevier Inc. All rights reserved.