Apoptosis induces neuronal apolipoprotein-E synthesis and localization in apoptotic bodies
Apoptosis induces neuronal apolipoprotein-E synthesis and localization in apoptotic bodies
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DOI：
10.1016/j.neulet.2007.02.014
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发表时间：
2007-04-12
影响因子：
2.5
通讯作者：
Garner, Brett
中科院分区：
文献类型：
--
作者：
Elliott, David A.;Kim, Woojin S.;Garner, Brett
神经元凋亡对中枢神经系统发育至关重要，也有助于神经退行性疾病。载脂蛋白-E（apoE）调节脑脂质转运和特定神经元功能，并且先前的研究，调查非神经元细胞类型，确定了细胞凋亡和apoE表达增加之间的关联。在本研究中，我们使用的人SK-N-SH神经元细胞系，以探讨潜在的变化apoE表达在细胞凋亡过程中发生的结果，延长培养（长达5天），而不补充营养因子。标准和实时PCR分析表明，apoE mRNA在3天后显著增加6倍，这与caspase-3活化、TUNEL阳性和凋亡小体形成相关。ApoE蛋白水平在没有细胞凋亡的情况下是低的，但当诱导细胞凋亡时增加了8倍。对培养上清液中积累的细胞碎片的分析表明，apoE水平逐渐集中在凋亡小体中。这些数据表明，apoE是上调神经元凋亡过程中，并提高apoE可能通过apoE-受体相互作用的凋亡小体的清除中发挥作用的可能性。(c)2007爱思唯尔爱尔兰有限公司保留所有权利。
Neuronal apoptosis is crucial for central nervous system development and also contributes to neurodegenerative disease. Apolipoprotein-E (apoE) regulates brain lipid transport and specific neuronal functions and previous research, investigating non-neuronal cell types, identified an association between apoptosis and increased apoE expression. In the present study we used the human SK-N-SH neuronal cell line to investigate potential changes in apoE expression during apoptosis which occurs as a consequence of extended culture (up to 5 days) without replenishing trophic factors. Standard and real-time PCR analysis indicated a significant 6-fold increase in apoE mRNA after 3 days which was correlated with caspase-3 activation, TUNEL positivity and the formation of apoptotic bodies. ApoE protein levels were low in the absence of apoptosis but increased by 8-fold when apoptosis was induced. Analysis of cellular debris that accumulated in the culture supernatants indicated that apoE levels became progressively concentrated in apoptotic bodies. These data indicate that apoE is up-regulated during neuronal apoptosis and raise the possibility that apoE may play a role in the clearance of apoptotic bodies through apoE-receptor interactions. (c) 2007 Elsevier Ireland Ltd. All rights reserved.