Effects of protein glycation and protective mechanisms against glycative stress.

ABSTRACT

Glycation is a posttranslational modification of proteins that contributes to the vast array of biological information that can be conveyed via a singular proteome. Understanding the role of advanced glycation end-products (AGEs) in human health and pathophysiology can be difficult, as the physiological effects of AGEs have been associated with multiple biological processes and disease state development, including acute myocardial ischemia-reperfusion injury, heart failure, and atherosclerosis, as well as tumor cell migration. The critical role of the glyoxalase system in the detoxification of methylglyoxal and other AGEs has been well established. Recently, evidence has emerged that DJ-1 displays antiglycative activity and may contribute to another mechanism of protection against protein glycation outside of the glyoxalase system. Identification of potential substrates of DJ-1 and determination of the pathways in which DJ-1 operates, is needed to fully understand the role of this protein in modulating biological homeostasis and the development of disease.