Assessment of old and new proteins: a novel methodology

Abstract

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.

Keywords: Individual proteins; Isotope tracer; Protein; Synthesis; Turnover.