Brefeldin A-induced neurotoxicity in cultured spinal cord neurons
Brefeldin A-induced neurotoxicity in cultured spinal cord neurons
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DOI：
10.1002/jnr.10479
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发表时间：
2003-02-15
影响因子：
4.2
通讯作者：
Tashiro, K
中科院分区：
文献类型：
--
作者：
Kikuchi, S;Shinpo, K;Tashiro, K
布雷菲德菌素A（Brefeldin A，BFA）是一种真菌代谢产物，已知其引起暴露细胞中高尔基复合体的分解和凋亡，这两者已被认为在神经退行性疾病，特别是肌萎缩性侧索硬化症（ALS）的发病机制中起作用。本研究表明，BFA对培养的大鼠脊髓神经元产生神经毒性和细胞核凋亡，并呈剂量和时间依赖性。脊髓运动神经元更容易受到这种神经毒性的影响。培养的脊髓神经元显示不可逆的解体高尔基体早在1小时后暴露于BFA。BFA诱导caspase-12的表达和激活开始后8小时曝光。在加入BFA后12小时，半胱天冬酶-3的裂解形式的水平增加。自由基的产生和线粒体膜电位的损失被观察到的后期阶段的神经毒性引起的BFA。总的来说，我们的数据表明，BFA是一个很好的代理再现ALS的病理生理特征。这种体外模型可能是有用的，试图研究这种神经退行性疾病的机制，并检查治疗潜力。(C)2002 Wiley-Liss，Inc.
Brefeldin A (BFA) is a fungus metabolite that is known to cause the disassembly of the Golgi complex and apoptosis in exposed cells, both of which have been suggested as playing roles in the pathogenesis of neurodegenerative diseases, particularly amyotrophic lateral sclerosis (ALS). This study showed that BFA caused neurotoxicity and apoptotic nuclear changes in cultured spinal neurons of rat spinal cord in a dose- and time-dependent manner. The spinal motor neurons were more vulnerable to this neurotoxicity. The cultured spinal neurons showed irreversible disassembly of the Golgi apparatus as early as 1 hr after exposure to BFA. BFA induced the expression and activation of caspase-12 beginning 8 hr after exposure. The level of the cleaved form of caspase-3 had increased 12 hr after the addition of BFA. Free radical generation and loss of mitochondrial membrane potential were observed in the later stages of neurotoxicity caused by BFA. Collectively, our data suggests that BFA is an excellent agent for reproducing the pathophysiological features of ALS. This in vitro model may be useful in attempts to study the mechanisms of this neurodegenerative disease and to examine therapeutic potentials. (C) 2002 Wiley-Liss, Inc.