Inhibitory effect of tartrate against phosphate-induced DJ-1 aggregation
- 주제(키워드) Tartrate , DJ-1 , Parkinson's disease , Inorganic phosphate , ROS
- 주제(기타) Biochemistry & Molecular Biology; Chemistry, Applied; Polymer Science
- 설명문(일반) [Kim, Min Soo; Jin, Wook] Gachon Univ, Sch Med, Dept Biochem, Lab Mol Dis & Cell Regulat, Incheon 21999, South Korea; [Lee, Sangmin] Korea Inst Ocean Sci & Technol, Marine Biotechnol Res Ctr, Ansan 15627, South Korea; [Lee, Sangmin] Kangwon Natl Univ, Dept Biochem, Coll Nat Sci, Chunchon 24341, South Korea; [Yun, Sanguk] Yale Univ, Dept Internal Med, Yale Cardiovasc Res Ctr, New Haven, CT 06520 USA; [Suh, Pann-Ghill] Ulsan Natl Inst Sci & Technol, Sch Life Sci, Ulsan 44919, South Korea; [Park, Jongmi; Cui, Minghua; Choi, Sun] Ewha Womans Univ, Coll Pharm, Seoul 03760, South Korea; [Park, Jongmi; Cui, Minghua; Choi, Sun] Ewha Womans Univ, Grad Sch Pharmaceut Sci, Seoul 03760, South Korea; [Cha, Sun-Shin] Ewha Womans Univ, Dept Chem & Nanosci, Seoul 03760, South Korea; [Jin, Wook] Gil Med Ctr, Gachon Med Res Inst, Incheon 21565, South Korea
- 등재 SCIE, SCOPUS
- 발행기관 ELSEVIER SCIENCE BV
- 발행년도 2018
- URI http://www.dcollection.net/handler/ewha/000000151608
- 본문언어 영어
- Published As http://dx.doi.org/10.1016/j.ijbiomac.2017.10.022
초록/요약
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.
more