mfat-1 transgene protects cultured adult neural stem cells against cobalt chloride-mediated hypoxic injury by activating Nrf2/ARE pathways
mfat-1 transgene protects cultured adult neural stem cells against cobalt chloride-mediated hypoxic injury by activating Nrf2/ARE pathways
复制标题
mfat-1转基因通过激活Nrf2/ARE途径保护培养的成体神经干细胞免受氯化钴介导的缺氧损伤
DOI：
10.1002/jnr.24096
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发表时间：
2018
影响因子：
4.2
通讯作者：
Dai Yifan
中科院分区：
文献类型：
--
作者：
Yu Junfeng;Yang Haiyuan;Fang Bin;Zhang Zhengwei;Wang Ying;Dai Yifan
缺血性中风是一种毁灭性的神经疾病，是成人死亡和严重残疾的主要原因之一。成人神经干细胞(NSC)替代疗法是一种很有前途的神经结构和功能恢复的治疗方法。然而，为了使治疗有效，必须保护成年神经干细胞免受缺血半暗带的缺氧缺血损伤。本研究旨在探讨转基因MFAT-1对氯化钴(CoCl2)诱导的成年神经干细胞缺氧缺血损伤的神经保护作用及其机制。结果表明，在CoCl2诱导的NSCs缺氧缺血损伤模型中，转基因脂肪-1可提高成年NSCs的活力，抑制CoCl2介导的成年NSCs的凋亡。此外，MFAT-1转基因促进了神经干细胞的增殖，成年神经干细胞的溴脱氧尿嘧啶核苷标记增加。这一过程与活性氧物种的还原有关。实时定量聚合酶链式反应和Western印迹分析显示核因子红系相关因子2(Nrf2)及其下游基因(HO-1、NQO-1、GCLC)的表达显著增加。综上所述，我们的研究结果表明，MFAT-1转基因通过激活核因子红系相关因子2(NRF2)/抗氧化反应元件(ARE)信号通路来抑制氧化应激损伤，从而恢复了CoCl2抑制的NSCs的活性和增殖。进一步研究MFAT-1转基因在成人保护机制中的作用可能会加速成人NSC替代治疗缺血性卒中的发展。
Ischemic stroke is a devastating neurological disorder and one of the leading causes of death and serious disability in adults. Adult neural stem cell (NSC) replacement therapy is a promising treatment for both structural and functional neurological recovery. However, for the treatment to work, adult NSCs must be protected against hypoxic‐ischemic damage in the ischemic penumbra. In the present study, we aimed to investigate the neuroprotective effects of the mfat‐1 transgene on cobalt chloride (CoCl2)‐induced hypoxic‐ischemic injury in cultured adult NSCs as well as its underlying mechanisms. The results show that in the CoCl2‐induced hypoxic‐ischemic injury model, themfat‐1transgene enhanced the viability of adult NSCs and suppressed CoCl2‐mediated apoptosis of adult NSCs. Additionally, the mfat‐1 transgene promoted the proliferation of NSCs as shown by increased bromodeoxyuridine labeling of adult NSCs. This process was related to the reduction of reactive oxygen species. Quantitative real‐time polymerase chain reaction and Western blot analysis revealed a much higher expression of nuclear factor erythroid 2‐related factor 2 (Nrf2) and its downstream genes (HO‐1,NQO‐1,GCLC). Taken together, our findings show that the mfat‐1 transgene restored the CoCl2‐inhibited viability and proliferation of NSCs by activating nuclear factor erythroid 2‐related factor 2 (Nrf2)/antioxidant response elements (ARE) signal pathway to inhibit oxidative stress injury. Further investigation of the function of the mfat‐1 transgene in adult protective mechanisms may accelerate the development of adult NSC replacement therapy for ischemic stroke.