Melatonin protects N2a against ischemia/reperfusion injury through autophagy enhancement
Melatonin protects N2a against ischemia/reperfusion injury through autophagy enhancement
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DOI：
10.1007/s11596-010-0101-9
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发表时间：
2010-02-01
影响因子：
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通讯作者：
Duan, Qiuhong
中科院分区：
文献类型：
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作者：
Guo, Yanchun;Wang, Jianfei;Duan, Qiuhong
研究表明，褪黑激素在缺血/再灌注介导的损伤中具有神经保护作用。尽管褪黑激素被认为是一种有效的抗氧化剂，但其保护机制不能仅用抗氧化来解释。这项研究致力于通过调查褪黑激素是否通过提高自噬来保护缺血/再灌注损伤的神经元来探索其他现有机制，因为自噬经常被认为在神经元存活中发挥着至关重要的作用。为了找到答案，建立了 N2a 细胞缺血/再灌注模型进行检查。结果表明，经褪黑素处理的 N2a 细胞在缺血后再灌注开始时自噬显着增强，并极大地促进了细胞存活，而通过 MTT、透射电子显微镜和激光共聚焦扫描显微镜评估，3-MA 阻断自噬导致 N2a 细胞存活缩短。此外，免疫印迹显示，在褪黑素存在下，缺血/再灌注损伤的 N2a 中 LC3II 和 Beclin1 的蛋白水平显着升高，而 PI3K/PKB 信号通路中的关键激酶 p-PKB 的表达与未治疗的受试者相比有所下降。综上所述，这些数据表明自噬可能是褪黑激素神经保护的机制之一。
Researches have shown that melatonin is neuroprotectant in ischemia/reperfusion-mediated injury. Although melatonin is known as an effective antioxidant, the mechanism of the protection cannot be explained merely by antioxidation. This study was devoted to explore other existing mechanisms by investigating whether melatonin protects ischemia/reperfusion-injured neurons through elevating autophagy, since autophagy has been frequently suggested to play a crucial role in neuron survival. To find it out, an ischemia/reperfusion model in N2a cells was established for examinations. The results showed that autophagy was significantly enhanced in N2a cells treated with melatonin at reperfusion onset following ischemia and greatly promoted cell survival, while autophagy blockage by 3-MA led to the shortened N2a cell survival as assessed by MTT, transmission electron microscopy, and laser confocal scanning microscopy. Besides, the protein levels of LC3II and Beclin1 were remarkably increased in ischemia/reperfusion-injured N2a in the presence of melatonin, whereas the expression of p-PKB, key kinase in PI3K/PKB signaling pathway, showed a decrease when compared with untreated subjects as accessed by immunoblotting. Taken together these data suggest that autophagy is possibly one of the mechanisms underlying neuroprotection of melatonin.