College of Arts and Science, Beijing Union University, Beijing 100191, China.
Bioorg Med Chem Lett. 2010 May 15;20(10):3084-8. doi: 10.1016/j.bmcl.2010.03.105. Epub 2010 Apr 2.
A large number of evidence has suggests that dyshomeostasis of the redox-active biometals such as copper and other metal ions can lead to oxidative stress in neurons, which plays a key role in the pathology of neurodegenerative disorders. Chitooligosaccharides (COSs) are biodegradation product of chitosan and demonstrated diverse biological activities, Here we first report that protective effects of COSs (M.W. 1500, DD. 90%) against Cu(II) induced neurotoxicity in primary cultured rat cortical neurons. The toxicity of Cu(II) to cortical neurons was obviously attenuated in a concentration-dependent manner by COSs pretreated. The data derived from lactate dehydrogenase (LDH) release and the Hoechst 33342 assay support the results from MTT assay. After DCFH assay, COSs were found to depress Cu(II) induced elevation in intracellular reactive oxygen species (ROS), These findings suggest that COSs protect against Cu(II) induced neurotoxicity in primary cortical neurons by interfering with an increase in intracellular reactive oxygen species (ROS).
大量证据表明，氧化还原活性生物金属（如铜和其他金属离子）的动态平衡失调会导致神经元氧化应激，这在神经退行性疾病的发病机制中起着关键作用。壳寡糖（COSs）是壳聚糖的生物降解产物，具有多种生物学活性。在这里，我们首次报道了 COSs（MW 1500，DD 90%）对原代培养的大鼠皮质神经元中 Cu（II）诱导的神经毒性的保护作用。COSs 预处理以浓度依赖的方式明显减轻 Cu（II）对皮质神经元的毒性。来自乳酸脱氢酶（LDH）释放和 Hoechst 33342 测定的数据支持 MTT 测定的结果。DCFH 测定后发现，COSs 可抑制 Cu（II）诱导的细胞内活性氧（ROS）升高。这些发现表明，COSs 通过干扰细胞内活性氧（ROS）的增加来保护原代皮质神经元免受 Cu（II）诱导的神经毒性。
