维生素C保护Aβ_(1-40)Cu(Ⅱ)复合物引起的神经元氧化损伤  

Protective Effects of Vitamin C Against Oxidative Stress Induced by Aβ_(1-40)Cu(Ⅱ) Complexes

作　　者：戴雪伶[1] 孙雅煊[2] 姜招峰[2] 

机构地区：[1]首都师范大学生命科学学院,北京100037 [2]北京联合大学应用文理学院,北京100083

出　　处：《中国生物化学与分子生物学报》2007年第7期586-591,共6页Chinese Journal of Biochemistry and Molecular Biology

基　　金：北京市教委科技发展项目;北京市自然科学基金重点项目(No.KZ200311417015);北京市属市管高校拔尖创新人才项目资助~~

摘　　要：老年斑中存在大量β-淀粉样蛋白(β-amyloid,Aβ)是老年痴呆症(Alzheimer′sdisease,AD)的重要病理特征.大量数据表明,Aβ上具有与过渡态金属离子共价结合的位点,二者能结合成为寡聚复合物.Aβ1-40Cu(Ⅱ)复合物通过Cu2+的还原催化O2产生H2O2,但反应机制不清.本文尝试以天然抗氧化剂维生素C(VC)来对抗Aβ1-40及Aβ1-40Cu(Ⅱ)复合物产生的H2O2对原代培养的神经细胞的毒性.结果表明,VC能够起到显著的保护作用,其有效浓度为1mmol/L.本文用胞外乳酸脱氢酶泄漏量和H2O2生成量的数据证实了细胞存活率(MTT实验)的实验结果.这些结果表明,Aβ1-40Cu(Ⅱ)复合物能够释放更多的H2O2,引发细胞膜破裂并最终引起细胞死亡.加入VC后,神经元受到的损伤较轻,提示VC在保护细胞免受氧化损伤方面发挥了重要作用.An important pathologic hallmark of Alzheimer＇s disease （AD） is senile plaque that mainly consists of β-amyloid （Aβ） peptide. Mounting evidence show that Aβ can form oligomeric complexes via binding transitional metal ions, such as Cu（Ⅱ ） and Fe（Ⅲ ）. Aβ1-40Cu（ Ⅱ ） complexes generate neurotoxic H2O2 from O2 via Cu^2＋ reduction, though the precise reaction mechanism is unclear. In the present study, vitamin C was used to abolish the cytotoxicity that was induced by Aβ1-40 or the Aβ1-40Cu（ Ⅱ ）complexes to cultured primary cortical neurons. The results favor markedly protective effects of vitamin C on injured neurons with the effective concentration being 1 mmol/L. The data derived from lactate dehydrogenase （LDH） released and the production of H2 02 were in accordance with the results obtained from the MTT assay, which indicated that binding of copper to Aβ1-40 increased the production of H2O2, leading to a breakdown in the integrity of the plasma membrane and eventually cell death. By contrast, neurons treated with vitamin C exhibited much slighter such damage. These results suggest that vitamin C plays a key role in protecting cells from oxidative damage.

关 键 词：AΒ1-40 Aβ1-40Cu(Ⅱ)复合物 维生素C H2O2 

分 类 号：Q51[生物学—生物化学]