Pretreatment of Mouse Neural Stem Cells with Carbon Monoxide-Releasing Molecule-2 Interferes with NF-kappa B p65 Signaling and Suppresses Iron Overload-Induced Apoptosis
Pretreatment of Mouse Neural Stem Cells with Carbon Monoxide-Releasing Molecule-2 Interferes with NF-kappa B p65 Signaling and Suppresses Iron Overload-Induced Apoptosis
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用一氧化碳释放分子 2 预处理小鼠神经干细胞可干扰 NF-kappa B p65 信号传导并抑制铁过载诱导的细胞凋亡
DOI：
10.1007/s10571-016-0333-8
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发表时间：
2016
影响因子：
4
通讯作者：
Bian Liuguan
中科院分区：
文献类型：
--
作者：
Xie Zhengxing;Han Ping;Cui Zhenwen;Wang Baofeng;Zhong Zhihong;Sun Yuhao;Yang Guoyuan;Sun Qingfang;Bian Liuguan
神经干细胞(NSC)移植是修复出血性卒中后受损脑组织的一种很有前途的方法，但供体细胞存活率低在很大程度上限制了它的应用。血肿的分解产物和随之而来的铁超载会损害神经细胞的存活。关于移植细胞死亡的机制方面的信息很少。此外，旨在提高移植的神经干细胞(NSCs)存活率的治疗研究明显缺乏。在这里，我们发现铁超载诱导了C17.2细胞的凋亡，C17.2细胞最初是从小鼠神经干细胞克隆而来的，并被v-myc永生化。一氧化碳释放分子-2(CORM-2)对C17.2细胞铁超载有明显的保护作用，且呈剂量依赖关系。此外，CORM-2干扰了NF-κB信号转导，包括抑制核转位和下调NF-κB p65的表达。TUNEL染色显示，CORM-2预处理C17.2细胞后，细胞对铁超载诱导的细胞凋亡的抵抗力增强，同时促凋亡蛋白Bax和裂解的caspase-3表达下调，抗凋亡蛋白Bcl2表达上调。CORM-2的保护作用可用NF-κB p65的特异性抑制剂BAY11-7082来模拟。这些结果为提高神经干细胞移植后的存活率提供了一种新的有效策略，从而提高了其修复出血性中风所致脑损伤的效果。
Neural stem cell (NSC) transplantation is a promising approach to repair the damaged brain after hemorrhagic stroke; however, it is largely limited by the poor survival of donor cells. Breakdown products of the hematoma and subsequent iron overload contribute to the impairment of survival of neural cells. There is little information regarding the mechanism involved in the death of grafted cells. Furthermore, therapeutic research targeted to improving the survival of grafted neural stem cells (NSCs) is strikingly lacking. Here, we showed that iron overload induced apoptosis of C17.2 cells, a cell line originally cloned from mouse NSCs and immortalized by v-myc. Pretreatment with carbon monoxide-releasing molecule-2 (CORM-2) markedly protected C17.2 cells against iron overload in a dose-dependent manner. Moreover, CORM-2 interfered with NF-κB signaling, including inhibition of nuclear translocation and down-regulation of NF-κB p65. TUNEL staining showed that preconditioning C17.2 cells with CORM-2 enhanced their resistance to apoptosis induced by iron overload, which was concomitant with down-regulation of the pro-apoptotic proteins (Bax and cleaved caspase-3) and up-regulation of the anti-apoptotic protein Bcl2. The protective effect of CORM-2 could be simulated by BAY11-7082, a special inhibitor of NF-κB p65. These results provide a novel and effective strategy to enhance the survival of NSCs after transplantation and, therefore, their efficacy in repairing brain injury due to hemorrhagic stroke.