Changes in Protein Expression and Lysine Acetylation Induced by Decreased Glutathione Levels in Astrocytes

摘要: Astrocytes and neurons form a highly specialized functional unit, the loss or gain of astrocytic functions can influence initiation progression different neurodegenerative diseases. Neurons depend on antioxidant protection provided by neighboring astrocytes. Glutathione (γ-l-glutamyl-l-cysteinyl-glycine) is major component system that defends cells against toxic effects reactive oxygen/nitrogen species. A decline in glutathione levels has been observed aging diseases, it aggravates pathology an amyotrophic lateral sclerosis-mouse model. Using SILAC-based quantitative proteomic approach, we analyzed changes global protein expression lysine acetylation primary astrocyte cultures obtained from wild-type mice those deficient glutamate-cysteine ligase modifier subunit (GCLM). GCLM knockout astrocytes display ∼80% reduction total levels. We identified potential molecular targets novel sites are affected chronic decrease response mediated Nrf2 activation. In addition, sequence analysis peptides displaying increased revealed enrichment cysteine residues vicinity site, which suggests crosstalk between lysine-acetylation modification. Regulation several metabolic pathways was at level acetylation, revealing coordinated involving transcriptional posttranslational regulation.