Inhibitory effect of tartrate against phosphate-induced DJ-1 aggregation

Abstract

The DJ-1 protein engages in diverse cellular and pathological processes, including tumorigenesis, apoptosis, sperm fertilization, and the progression of Parkinson's disease (PD). The functional dimeric form of DJ-1 transforms into non-functional filamentous aggregates in an inorganic phosphate (P-1)-dependent manner in vitro. Here, we demonstrated that P-i and reactive oxygen species (ROS) induce DJ-1 aggregation in Neuro2A and SH-SY5Y cells. Remarkably, tartrate treatment significantly reduced P-i- and ROS-induced DJ-1 aggregation and restored P-i- and ROS-provoked cell death using quantitative data as mean +/- standard deviation, and statistics. Mechanistically, tartrate prevented DJ-1 aggregation via occupying the P-i-binding site. These findings revealed an unexpected physiological role of tartrate in the maintenance of DJ-1 function, and thus, a potential use as an inhibitor of DJ-1 aggregation. (C) 2017 Elsevier B.V. All rights reserved.