Succinylation proteome analysis of Cd-exposed Neuro-2a cells

ABSTRACT: Cadmium is a neurotoxic compound which induces cognitive alterations similar to those produced by Alzheimer's disease (AD). Autophagic flux impairment is a hallmark in Cd-induced AD-like pathology. However, the underlying mechanism remains obscure. In these study, Neuro-2a cells were exposed to different concentrations of Cd (1, 2, and 4 μM) for 72 h, and C57 mice (8 week) were orally administered Cd for 12 weeks. Chronic Cd exposure inhibited autophagosome-lysosome fusion and impaired lysosomal function, thereby contributing to defects in autophagic clearance and subsequently leading to APP accumulation and nerve cell death. Mechanistically, proteomic analysis coupled with Ingenuity Pathway Analysis identified the crucial key target molecule in Cd-impaired autophagic flux. Four-dimensional label-free succinylation quantitative proteomics were performed in Neuro-2a cells with and without 4 μM CdCl2 treatment for 72h. Then, vital molecules and crucial succinylation sites were identified. Moreover, the function and important role of the resulting molecule with crucial succinylation site were determined. These results may thus open an avenue for therapeutic intervention in chronic Cd-induced AD-like pathology.

INSTRUMENT(S): timsTOF Pro

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Cell Culture

SUBMITTER: Huifeng Pi  

LAB HEAD: Huifeng Pi

PROVIDER: PXD048158 | Pride | 2024-10-17

REPOSITORIES: Pride