Wilkins Heather M, Koppel Scott J, Bothwell Rebecca, Mahnken Jonathan, Burns Jeffrey M, Swerdlow Russell H
Department of Neurology University of Kansas Medical Center, Kansas City, KS, USA; University of Kansas Alzheimer's Disease Center, Kansas City, KS, USA.
University of Kansas Alzheimer's Disease Center, Kansas City, KS, USA.
Redox Biol. 2017 Aug;12:828-832. doi: 10.1016/j.redox.2017.04.010. Epub 2017 Apr 13.
A degradation product of APOE ε4-encoded apolipoprotein E protein targets mitochondria and inhibits cytochrome oxidase (COX), and autopsy brains from young adult APOE ε4 carriers show reduced COX activity. To further explore relationships between APOE alleles and COX, we measured platelet mitochondria COX activity in AD subjects with (n=8) and without (n=7) an APOE ε4 allele and found the mean COX activity, when normalized to sample total protein, was lower in the APOE ε4 carriers (p<0.05). Normalizing COX activity to citrate synthase (CS) activity eliminated this difference, but notably the mean CS activity was itself lower in the APOE ε4 carriers (p<0.05). COX and CS protein levels did not appear to cause the lower APOE ε4 carrier COX and CS Vmax activities. If confirmed in larger studies, these data could suggest mitochondria at least partly mediate the well-recognized association between APOE alleles and AD risk.
APOE ε4编码的载脂蛋白E蛋白的一种降解产物靶向线粒体并抑制细胞色素氧化酶（COX），并且来自年轻成年APOE ε4携带者的尸检大脑显示COX活性降低。为了进一步探究APOE等位基因与COX之间的关系，我们测量了有（n = 8）和无（n = 7）APOE ε4等位基因的AD受试者的血小板线粒体COX活性，发现当以样品总蛋白进行标准化时，APOE ε4携带者的平均COX活性较低（p<0.05）。将COX活性以柠檬酸合酶（CS）活性进行标准化消除了这种差异，但值得注意的是，APOE ε4携带者中CS的平均活性本身较低（p<0.05）。COX和CS蛋白水平似乎并未导致APOE ε4携带者较低的COX和CS最大反应速度活性。如果在更大规模的研究中得到证实，这些数据可能表明线粒体至少部分介导了APOE等位基因与AD风险之间广为人知的关联。
