Se-Methylselenocysteine Inhibits Apoptosis Induced by Clusterin Knockdown in Neuroblastoma N2a and SH-SY5Y Cell Lines

Se-Methylselenocysteine Inhibits Apoptosis Induced by Clusterin Knockdown in Neuroblastoma N2a and SH-SY5Y Cell Lines
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Se-甲基硒代半胱氨酸抑制神经母细胞瘤 N2a 和 SH-SY5Y 细胞系中簇蛋白敲低诱导的细胞凋亡

DOI:
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发表时间:
2014
影响因子:
5.6
通讯作者:
Jiazuan Ni
Jiazuan Ni
中科院分区:
生物学2区
文献类型:
--
作者:
Chao Wang;Z. Zeng;Qiong Liu;Renli Zhang;Jiazuan Ni

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细胞凋亡作为一种程序性细胞死亡过程,对维持生物体的组织功能至关重要。这一过程的改变与许多疾病有关。clusterin(Clu)过表达可拮抗多种细胞的凋亡。硒(Se)是人体必需的微量元素。其生物学功能也与细胞凋亡有关。为探讨Clu在细胞凋亡过程中的作用及Se对细胞凋亡的影响,设计了两组短发夹RNA(short-hairpin RNA,shRNA)重组质粒,分别转染小鼠神经母细胞瘤N2 a细胞(N2 a细胞)和慢病毒感染人神经母细胞瘤SH-SY 5 Y细胞(SH-SY 5 Y细胞)。这些shRNA在mRNA和蛋白质水平上特异有效地干扰Clu的细胞内表达。Clu基因敲低的细胞表现出凋亡相关的特征,包括抗氧化能力和Bcl-2/Bax比值下调和caspase-8活性上调。1 μM的Se-甲基硒代半胱氨酸(MSC)可逆转Clu-敲低引起的抗氧化能力、Bcl 2/Bax比值和caspase-8活性的改变,从而抑制细胞凋亡,维持细胞活力。提示Clu和Se具有神经保护作用。
Apoptosis, as a programmed cell death process, is essential for the maintenance of tissue function in organisms. Alteration of this process is linked to many diseases. Over-expression of clusterin (Clu) can antagonize apoptosis in various cells. Selenium (Se) is an essential trace element for human health. Its biological function is also associated with cell apoptosis. To explore the function of Clu and the impact of Se in the process of apoptosis, several short-hairpin RNAs (shRNA) were designed for the construction of two sets of recombinant plasmids: one set for plasmid-transfection of mouse neuroblastoma N2a cells (N2a cells); and the other set for lentiviral infection of human neuroblastoma SH-SY5Y cells (SH-SY5Y cells). These shRNAs specifically and efficiently interfered with the intracellular expression of Clu at both the mRNA and protein levels. The Clu-knockdown cells showed apoptosis-related features, including down-regulation of antioxidative capacity and the Bcl-2/Bax ratio and up-regulation of caspase-8 activity. Se-methylselenocysteine (MSC) at an optimum concentration of 1 μM could reverse the alteration in antioxidative capacity, Bcl2/Bax ratio and caspase-8 activity caused by Clu-knockdown, thus inhibiting apoptosis and maintaining cell viability. The results hereby imply the potentiality of Clu and Se in neuroprotection.
血管紧张素刺激肾积水新生大鼠肾脏中的 TGF-β1 和簇蛋白。
DOI: 10.1152/ajpregu.2000.278.3.r640
发表时间: 2000
期刊: American journal of physiology. Regulatory, integrative and comparative physiology
影响因子: --
作者:
Yoo,KH;Thornhill,BA;Chevalier,RL
通讯作者: Chevalier,RL