Pomalidomide Ameliorates H₂O₂-Induced Oxidative Stress Injury and Cell Death in Rat Primary Cortical Neuronal Cultures by Inducing Anti-Oxidative and Anti-Apoptosis Effects.
Pomalidomide Ameliorates H₂O₂-Induced Oxidative Stress Injury and Cell Death in Rat Primary Cortical Neuronal Cultures by Inducing Anti-Oxidative and Anti-Apoptosis Effects.
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DOI：
10.3390/ijms19103252
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发表时间：
2018-10-19
影响因子：
5.6
通讯作者：
Chen KY
中科院分区：
文献类型：
--
作者：
Tsai YR;Chang CF;Lai JH;Wu JC;Chen YH;Kang SJ;Hoffer BJ;Tweedie D;Luo W;Greig NH;Chiang YH;Chen KY
由于其高需氧量和丰富的过氧化易感脂质细胞，大脑特别容易受到氧化应激的影响。氧化应激是由氧化还原状态失衡引起的，包括活性氧（ROS）的过量产生或抗氧化系统的功能障碍，氧化应激在常见的病理生理学中起着核心作用，在急性神经系统疾病（以中风为代表）和慢性神经系统疾病（如阿尔茨海默病）中支撑神经元细胞死亡。例如，在脑缺血后，炎症在永久性神经损伤的发展中起着关键作用。ROS参与了缺血后炎症的发生机制。几种炎症酶的激活产生活性氧，活性氧随后抑制线粒体活性，导致进一步的组织损伤。波马度胺（Pomalidomide， POM）是一种临床可用的免疫调节剂和抗炎剂。通过h2o2处理的大鼠原代皮质神经元培养，我们发现POM对氧化应激和细胞死亡具有神经保护作用，这与核因子红系衍生2/超氧化物歧化酶2/过氧化氢酶信号通路的变化有关。POM还通过调节Bax、细胞色素c和多聚腺苷核糖（adp -核糖）聚合酶，抑制核因子kappa-轻链增强子（NF-κB）水平，显著减轻皮质神经元凋亡。综上所述，POM对h2o2诱导的损伤具有抗氧化和抗炎作用，具有神经保护作用。因此，POM代表了一种潜在的治疗脑损伤和相关疾病的药物，值得进一步评估。
Due to its high oxygen demand and abundance of peroxidation-susceptible lipid cells, the brain is particularly vulnerable to oxidative stress. Induced by a redox state imbalance involving either excessive generation of reactive oxygen species (ROS) or dysfunction of the antioxidant system, oxidative stress plays a central role in a common pathophysiology that underpins neuronal cell death in acute neurological disorders epitomized by stroke and chronic ones such as Alzheimer’s disease. After cerebral ischemia, for example, inflammation bears a key responsibility in the development of permanent neurological damage. ROS are involved in the mechanism of post-ischemic inflammation. The activation of several inflammatory enzymes produces ROS, which subsequently suppress mitochondrial activity, leading to further tissue damage. Pomalidomide (POM) is a clinically available immunomodulatory and anti-inflammatory agent. Using H2O2-treated rat primary cortical neuronal cultures, we found POM displayed neuroprotective effects against oxidative stress and cell death that associated with changes in the nuclear factor erythroid derived 2/superoxide dismutase 2/catalase signaling pathway. POM also suppressed nuclear factor kappa-light-chain-enhancer (NF-κB) levels and significantly mitigated cortical neuronal apoptosis by regulating Bax, Cytochrome c and Poly (ADP-ribose) polymerase. In summary, POM exerted neuroprotective effects via its anti-oxidative and anti-inflammatory actions against H2O2-induced injury. POM consequently represents a potential therapeutic agent against brain damage and related disorders and warrants further evaluation.
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影响因子：
6.1
作者：
Guo C;Sun L;Chen X;Zhang D
通讯作者：
Zhang D
影响因子：
7.3
作者：
Clark IA;Vissel B
通讯作者：
Vissel B
MicroRNAs 调节脑缺血再灌注损伤中的线粒体功能
影响因子：
5.6
作者：
Hu Y;Deng H;Xu S;Zhang J
通讯作者：
Zhang J
影响因子：
5.3
作者：
Chou, Szu-Yi;Weng, Ju-Yun;Chern, Yijuang
通讯作者：
Chern, Yijuang
影响因子：
9.3
作者：
Giunta B;Obregon D;Velisetty R;Sanberg PR;Borlongan CV;Tan J
通讯作者：
Tan J