Proteomic Analyses for the Global S -Nitrosylated Proteins in the Brain Tissues of Different Human Prion Diseases

We described the first proteomic analysis of globalS-nitrosylation in brain tissues of sporadic Creutzfeldt –Jakob disease (sCJD), fatal familial insomnia (FFI), and genetic CJD with a substitution of valine for glycine at codon 114 of the prion protein gene (G114V gCJD) accompanying with normal control with isobaric tags for relative and absolute quantitation (iTRAQ) combined with a nano-HPLC/Q-Exactiv e mass spectrometry platform. In parallel, we used several approaches to provide quality control for the experimentally definedS-nitrosylated proteins. A total of 1509S-nitrosylated proteins (SNO-proteins) were identified, and data are available via ProteomeXchange with identifier PXD002813. The cerebellum tissues appeared to contain more commonly differentially expressedSNO-proteins (DESPs) than cortex of sCJD, FFI, and gCJD. Three selectedSNO-proteins were verified by Western blots, consistent with proteomics assays. Gene ontology analysis showed that more up-regulated DESPs were involved in metabolism, cell cytoskeleton/structure, and immune system both in the cortex and cerebellum, while more down-regulated ones in both regions were involved in cell cytoskeleton/structure, cell-cell communication, and miscellaneous function protein. Pathway analysis suggested that systemic lupus erythematosus, pathogenicEscherichia coli infection, and extracellular matrix-receptor interaction were the most commonly affected pathways, which were identified from at least two different dise...
Source: Molecular Neurobiology - Category: Neurology Source Type: research