Nova1 mediates resistance of rat pheochromocytoma cells to hypoxia-induced apoptosis via the Bax/Bcl-2/caspase-3 pathway.

Nova1 mediates resistance of rat pheochromocytoma cells to hypoxia-induced apoptosis via the Bax/Bcl-2/caspase-3 pathway.
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Nova1通过Bax/Bcl-2/caspase-3途径介导大鼠嗜铬细胞瘤细胞对缺氧诱导的细胞凋亡的抵抗

DOI:
10.3892/ijmm.2017.3089
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发表时间:
2017-10
影响因子:
5.4
通讯作者:
Cui H
Cui H
中科院分区:
医学3区
文献类型:
--
作者:
Li H;Lv B;Kong L;Xia J;Zhu M;Hu L;Zhen D;Wu Y;Jia X;Zhu S;Cui H

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神经肿瘤腹侧抗原1(Nova 1)是一种众所周知的脑特异性剪接因子。几项研究已经确定Nova 1是一种位于分层网络顶部的调节蛋白。然而,Nova 1在缺氧期间的功能仍然知之甚少。本研究旨在探讨Nova 1对细胞缺氧的保护作用,并进一步探讨其可能的作用机制。缺氧过程中,嗜铬细胞瘤PC 12细胞存活率逐渐降低,凋亡率逐渐增加,在缺氧48 h时达到高峰。pCMV-Myc-Nova 1转染PC 12细胞48 h后,Nova 1的表达明显增强,广泛分布于细胞质和细胞核中。而且,细胞存活率显著提高,凋亡率显著降低。pCMV-Myc-Nova 1组Bax和caspase-3的mRNA和蛋白表达水平显著降低,而pCMV-Myc-Nova 1组Bax和caspase-3的mRNA和蛋白表达水平显著升高,Bcl-2的mRNA和蛋白表达水平显著降低,而pCMV-Myc-Nova 1组Bcl-2的mRNA和蛋白表达水平显著升高。本研究提示Nova 1可能通过Bax/Bcl-2/caspase-3通路参与了缺氧诱导的PC 12细胞凋亡抵抗,这一发现对于探索缺氧的新机制和缺氧相关疾病的治疗具有重要意义。
Neuro-oncological ventral antigen 1 (Nova1) is a well known brain-specific splicing factor. Several studies have identified Nova1 as a regulatory protein at the top of a hierarchical network. However, the function of Nova1 during hypoxia remains poorly understood. This study aimed to investigate the protective effect of Nova1 against cell hypoxia and to further explore the Bax/Bcl-2/caspase-3 pathway as a potential mechanism. During hypoxia, the survival rate of pheochromocytoma PC12 cells was gradually decreased and the apoptosis rate was gradually increased, peaking at 48 h of hypoxia. At 48 h after transfection of PC12 cells with pCMV-Myc-Nova1, the expression of Nova1 was significantly increased, with wide distribution in the cytoplasm and nucleus. Moreover, the survival rate was significantly increased and the apoptosis rate was significantly decreased. Additionally, the mRNA and protein expression levels of Bax and caspase-3 were significantly increased in the pCMV-Myc group and significantly decreased in the pCMV-Myc-Nova1 group, whereas that of Bcl-2 was significantly decreased in the pCMV-Myc group and significantly increased in the pCMV-Myc-Nova1 group. This study indicated that Nova1 could be linked to resistance to the hypoxia-induced apoptosis of PC12 cells via the Bax/Bcl-2/caspase-3 pathway, and this finding may be of significance for exploring novel mechanisms of hypoxia and the treatment of hypoxia-associated diseases.
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发表时间: 2015
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