Jie Bai
Kunming University of Science and Technology, China
Title: Thioredoxin-1 suppresses MPP+/MPTP neurotoxicity through enhancing autophagy
Biography
Biography: Jie Bai
Abstract
Autophagy is a lysosomal degradative process used to recycle obsolete cellular constituents and eliminate damaged organelles and misfolded protein. Autophagy is associated with the pathogenesis of Parkinson’s disease(PD). Thioredoxin-1 (Trx-1) is a redox regulating protein and plays an important role in PD. However, the relationship between autophagy and Trx-1 in PD has not been reported. Cell and mouse models of PD were used to examine the relationship of autophagy and Trx-1. We showed that the expression of microtubule-associated protein light chain 3 (LC3-II), an autophagosome membrane marker, was induced by 1-Methyl-4-phenylpyridinium ion(MPP+)/1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP) in PC12 cells and mice. Rapamycin, autophagy inducer, decreased toxicity by MPP+, in contrast, chloroquine, autophagy inhibitor, increased toxicity by MPP+. These results suggest that autophagy plays a protecting role against MPP+ neurotoxicity. The overexpression of Trx-1 in PC12 cells and mice reversed LC3-II expression by MPP+/MPTP. Importantly, Forkhead box O3A(FOXO3A) expression was decreased by MPP+/MPTP in PC12 cells and substantia nigra pars compacta(SNpc) of mice. The decrease of FOXO3A was enhanced by downregulation of Trx-1 and reversed by Trx-1 overexpression in mice. These results suggest that Trx-1 suppresses MPP+/MPTP neurotoxicity by enhancing FOXO3A/autophagy pathway. Our present study indicates FOXO3A may be a new potential target for treatment of PD.