A Docosahexaenoic Acid-Derived Pro-resolving Agent, Maresin 1, Protects Motor Neuron Cells Death
A Docosahexaenoic Acid-Derived Pro-resolving Agent, Maresin 1, Protects Motor Neuron Cells Death
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DOI：
10.1007/s11064-018-2556-1
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发表时间：
2018-07-01
影响因子：
4.4
通讯作者：
Shimazawa, Masamitsu
中科院分区：
文献类型：
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作者：
Ohuchi, Kazuki;Ono, Yoko;Shimazawa, Masamitsu
Maresin 1是一种从二十二碳六烯酸（DHA）中提取的新型促溶解介质，对多种动物模型，包括脑缺血、败血症和肺纤维化具有有效的抗炎作用。然而，其对运动神经元细胞死亡的影响尚未被研究。因此，我们研究了maresin 1在几种应激性运动神经元细胞死亡中的作用。Maresin 1抑制超氧化物歧化酶1 (SOD1)（G93A）引起的组合应激和无血清诱导的运动神经元细胞死亡呈浓度依赖性，具有比DHA更强的神经保护作用。Maresin 1还对dna结合蛋白(TDP)-43（A315T）和无血清应激、H2O2和tunicamycin诱导的细胞死亡具有神经保护作用。Maresin 1降低了SOD1（G93A）或TDP-43（A315T）引起的活性氧（ROS）的产生。此外，marsin 1抑制SOD1（G93A）和无血清应激诱导的NF-kappa B活化。这些数据表明，maresin 1通过减少ROS的产生或抑制NF-kappa B的激活，对运动神经元具有多种应激保护作用。Maresin 1对H2O2和tunicamycin诱导的细胞死亡也有神经保护作用，且呈浓度依赖性。最后，maresin 1改善了内质网应激上调的脊髓性肌萎缩模型的运动功能缺陷。因此，马氏蛋白1可能有助于预防运动神经元疾病。
Maresin 1 is a novel pro-resolving mediator derived from docosahexaenoic acid (DHA), with potent anti-inflammation effects against several animal models, including brain ischemia, sepsis, and lung fibrosis. However, its effect against motor neuron cell death is still not investigated. Therefore, we investigated the effects of maresin 1 on several stress-induced motor neuron cell death. Maresin 1 suppressed combinatorial stress which was evoked by superoxide dismutase 1 (SOD1)(G93A) and serum-free, -induced motor neuron cells death in a concentration-dependent manner, and had a stronger neuroprotective effective than DHA. Maresin 1 also had neuroprotective effects against transactivation response DNA-binding protein (TDP)-43(A315T) and serum-free stress, H2O2, and tunicamycin-induced cell death. Maresin 1 reduced the reactive oxygen species (ROS) production caused by SOD1(G93A) or TDP-43(A315T). Moreover, maresin 1 suppressed the NF-kappa B activation induced by SOD1(G93A) and serum-free stress. These data indicate that maresin 1 has motor neuron protective effects against several stresses by reduction of ROS production or attenuation of the NF-kappa B activation. Maresin 1 also had neuroprotective effects against H2O2, and tunicamycin-induced cell death in a concentration-dependent manner. Finally, maresin 1 ameliorated the motor function deficits of spinal muscular atrophy model in which endoplasmic reticulum stress was upregulated. Thus, maresin 1 may be beneficial to protect against motor neuron diseases.