Department of Preclinical Sciences, Faculty of Medical Sciences, University of the West Indies, St. Augustine, Trinidad and Tobago.
J Mol Neurosci. 2011 Mar;43(3):284-9. doi: 10.1007/s12031-010-9436-8. Epub 2010 Aug 20.
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by high levels of aluminum and certain other metal ions in the brain: The disease is also characterized by low activity of brain cytochrome c oxidase (COX) but whether the elevated metal ions and the low COX activity are linked is not known. Moreover, COX is known to exhibit two catalytic rates (V (max)) and two substrate binding constants (K (m)) but it is not known which of these is affected in AD. In this study, we employed the Klatzo AD rabbit model to evaluate the impact of elevated metal ions on brain COX activity. New Zealand white rabbits were injected intra-cerebrally with 1.4% solutions of either AlCl(3), FeCl(3), CaCl(2), or MgCl(2); and 10 days, later the brain mitochondria were isolated. Polarographic assay revealed that compared to the controls, all four metals led to decreases in the V (max) of the enzyme's low affinity site. The respective decreases were; 16%, 36%, 18%, and 30%. The results suggest a sequence of events in vivo in which oxygen radical damage to mitochondria and COX leads to low ATP production and excess heme establishing conditions thought to be ideal for neurodegeneration.
阿尔茨海默病（AD）是一种神经退行性疾病，其特征是大脑中高水平的铝和某些其他金属离子：该疾病还表现为脑细胞色素 c 氧化酶（COX）活性低，但升高的金属离子和低 COX 活性是否相关尚不清楚。此外，COX 已知表现出两种催化速率（V（max））和两种底物结合常数（K（m）），但尚不清楚 AD 中受影响的是哪一种。在这项研究中，我们采用 Klatzo AD 兔模型来评估升高的金属离子对脑 COX 活性的影响。新西兰白兔脑内注射 1.4%的 AlCl3、FeCl3、CaCl2 或 MgCl2 溶液；10 天后，分离脑线粒体。极谱法测定显示，与对照组相比，所有四种金属都导致酶低亲和力部位的 V（max）降低。分别降低了 16%、36%、18%和 30%。结果表明，体内存在一系列事件，即氧自由基对线粒体和 COX 的损伤导致 ATP 产生减少和血红素过量，从而形成被认为是理想的神经退行性变条件。
