A quantitative proteomic analysis reveals the potential roles of PRDX3 in neurite outgrowth in N2a-APPswe cells

Abstract

Alzheimer's disease (AD) is characterized by amyloid plaques and neurofibrillary tangles accompanied by progressive neurite loss. Mitochondria play pivotal roles in AD development. PRDX3 is a mitochondrial peroxide reductase critical for H2O2 scavenging and signal transduction. In this study, we found that PRDX3 knockdown (KD) in the N2a-APPswe cell line promoted retinoic acid (RA)-induced neurite outgrowth but did not reduce the viability of cells damaged by tert-butyl hydroperoxide (TBHP). We found that knocking down PRDX3 expression induced dysregulation of more than one hundred proteins, as determined by tandem mass tag (TMT)-labeled proteomics. A Gene Ontology (GO) analysis revealed that the dysregulated proteins were enriched in protein localization to the plasma membrane, the lipid catabolic process, and intermediate filament cytoskeleton organization. A STRING analysis showed close protein–protein interactions among dysregulated proteins. The expression of Annexin A1 (ANXA1), serine (Ser)-/threonine (Thr)-protein phosphatase 2A catalytic subunit alpha isoform (PP2A) and glutathione S-transferase Mu 2 (GSTM2) was significantly upregulated in PRDX3-KD N2a-APPswe cell lines, as verified by western blotting. Our study revealed, for the first time, that PRDX3 may play important roles in neurite outgrowth and AD development.