The Role of DJ-1 in the Glycation Process of Skin and Plasma Proteins in Mice Models

Abstract

The glycation reaction is a non-enzymatic reaction characterized by and spontaneous binding of sugar molecules and protein. This study focuses on the glycation process at the level of proteins. Protein glycation is initiated by a condensation reaction between the carbonyl of a reducing sugar with the amino or thiol group of a protein. Advanced glycation end products (AGEs) are the byproduct of the glycation reaction. At the level of the proteins, AGEs are glycated cross-linked proteins that aggregate with time and lose their function. Glycation was classified as an irreversible one-way reaction until the preexisting DJ-1 chaperone protein was identified as a deglycase protein. Since DJ-1 is a highly conserved protein a DJ-1-derived protein called ND-13 was developed and presented agonistic activity to DJ-1. This study aims to investigate the role of DJ-1 in the glycation process of skin and plasma proteins in mice models to better understand the mechanism of action of DJ-1. AGEs formation was induced in mice models by either passive exposure to smoke and/or intraperitoneal D-ribose injection. Mice were then treated with ND-13 to identify through it the deglycase activity of DJ-1.Overall, the findings of this study indicate that the glycation process in the skin might need more than just a few weeks to form the early and intermediate glycation products, this was translated by the significant increase of DJ-1 levels after 8 weeks of treatment with an exogenous glycating agent compared to week 4. In comparison to the other groups, the group treated with ND-13 presented much higher levels of DJ-1 which suggest that ND-13 might present an additive agonistic effect to the endogenous deglycase DJ-1.In contrast, levels of DJ-1 were not detected at the level of the plasma, this might contribute by further demonstrating that DJ-1 might be an intracellular protein that under oxidative stress translocate into the nucleus or is excreted into the extracellular matrix of the tissue to protect act as an antioxidant and delicate protein to protect both environments. Therefore, our findings propose that DJ-1 might be upregulated by a significant increase in carbonyl stress in a time dependent manner, further contributing to the preexisting literature about the deglycase activity of DJ-1. However, more perspective studies are needed to identify tissue-specificity of DJ-1 protein.