肌酸对神经细胞硝化应激的保护作用

The protective effect of creatine on neurocyte under nitrosative stress

目的一氧化氮引发的神经兴奋性毒性作用是多种神经退行性疾病后期神经元溃变退行的共同途径。方法为探究肌酸对于神经兴奋性毒性的调节效应,利用一氧化氮供体GSNO处理SH-SY5Y神经细胞建立硝化应激条件,检测肌酸对于神经细胞硝化应激的保护作用并验证其作用机制。结果实验结果表明,肌酸的保护作用具有剂量依赖性效应,添加肌酸能显著提高硝化应激条件下神经细胞活力,降低神经细胞染色质凝结。研究发现,肌酸对于硝化应激的保护作用是通过肌酸激酶催化,以提升细胞能量荷载实现的。结论肌酸处理可显著提高应激条件下神经细胞内的ATP含量,降低AMPK磷酸化水平,且其保护作用可被肌酸激酶抑制剂DNFB所拮抗。

Objective Excitotoxiticiy triggered by nitric oxide is the common and final degenerative pathway of neurons in many kinds of neurodegenerative diseases. Methods To investigate the intervention effect of creatine on neural excitotoxicity, the nitrosative stress model was established on SH-SY5Y neurocyte treated with GSNO, the nitric oxide donor. The protective effect and the underlying mechanism of creatine on the cell model was tested. Results Results showed that, creatine exhibited its protective role in a dose-dependent manner. Creatine was proved to increase the cell viability under introstive challenge significantly, and also reduced the chromatin condensation in the experiment. Results also showed that, creatine exerted the anti- nitrosative stress role through elevating the intracellular energy charge, which mediated by the catalysis of creatine kinase. Conclusion Creatine treatment could significantly promote the intracellular ATP content under nitrosative stress, and decrease the phosphorylation of AMPK. Meanwhile, the protective of creatine on neurocyte could be blocked by DNFB, the creatine kinase inhibitor.