Mayo Clinic, Division of Endocrinology, 200 First Street SW, Joseph 5-194, Rochester, MN 55905, USA.
Nutr Metab Cardiovasc Dis. 2013 Dec;23 Suppl 1(0 1):S6-11. doi: 10.1016/j.numecd.2012.05.006. Epub 2012 Jul 10.
Protein modifications and the accumulation of those proteins are implicated in a host of diseases from Parkinson's and Alzheimer's to both insulin independent and insulin dependent diabetes mellitus. Accumulation of irreversibly modified proteins occurs when the degradation rate of proteins is reduced or the rate of modification increases. Although the synthesis rates of individual proteins in vivo have been extensively studied the methodology to measure degradation rates of individual proteins in vivo remains to be well developed. However, the ability to measure the relative age of a particular protein pool in relation to the quality of the pool (amount of damage) is a recent advance. This brief review describes a novel methodology to simultaneously measure the synthesis rate of individual proteins along with the accumulation of oxidative damage to those proteins in vivo. The results of a recent investigation on individuals with type 1 diabetes mellitus are described. Accelerated damage to de novo synthesized ApoA-1 is shown during short-term insulin cessation, which has potential clinical implications. Future implications of the novel method in diabetes and aging are also discussed.
蛋白质修饰及其积累与多种疾病有关,包括帕金森病、阿尔茨海默病、非胰岛素依赖型和胰岛素依赖型糖尿病等。当蛋白质的降解率降低或修饰率增加时,不可逆修饰的蛋白质就会积累。虽然体内单个蛋白质的合成率已经得到了广泛的研究,但在体内测量单个蛋白质降解率的方法仍有待完善。然而,能够测量特定蛋白质库相对于蛋白质库质量(损伤程度)的相对年龄是最近的一项进展。本文简要综述了一种新的方法,可以同时测量个体蛋白质的合成率以及体内这些蛋白质的氧化损伤积累。本文还描述了对 1 型糖尿病患者的一项最新研究结果。在短期停止胰岛素治疗期间,新合成的 ApoA-1 受到加速损伤,这具有潜在的临床意义。本文还讨论了该新方法在糖尿病和衰老领域的未来意义。