Phosphoproteomic Analysis and Protein–Protein Interaction of Rat Aorta GJA1 and Rat Heart FKBP1A after Secoiridoid Consumption from Virgin Olive Oil: A Functional Proteomic Approach

Abstract

Protein functional interactions could explain the biological response of secoiridoids (SECs), main phenolic compounds in virgin olive oil (VOO). The aim was to assess protein–protein interactions (PPIs) of the aorta gap junction alpha-1 (GJA1) and the heart peptidyl-prolyl cis-trans isomerase (FKBP1A), plus the phosphorylated heart proteome, to describe new molecular pathways in the cardiovascular system in rats using nanoliquid chromatography coupled with mass spectrometry. PPIs modified by SECs and associated with GJA1 in aorta rat tissue were calpain, TUBA1A, and HSPB1. Those associated with FKBP1A in rat heart tissue included SUCLG1, HSPE1, and TNNI3. In the heart, SECs modulated the phosphoproteome through the main canonical pathways PI3K/mTOR signaling (AKT1S1 and GAB2) and gap junction signaling (GAB2 and GJA1). PPIs associated with GJA1 and with FKBP1A, the phosphorylation of GAB2, and the dephosphorylation of GJA1 and AKT1S1 in rat tissues are promising protein targets promoting cardiovascular protection to explain the health benefits of VOO.

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“…Complete information on the next steps of the proteomic and phosphoproteomic analyses: peptide 11-plex TMT labelling, nanoLC-(Orbitrap)MS/MS analysis, protein identification/quantification, phosphopeptide enrichment and statistical analysis, are detailed in the ESI† section and previously described. 15,24…”

“…Complete information on the next steps of the proteomic and phosphoproteomic analyses: peptide 11-plex TMT labelling, nanoLC-(Orbitrap)MS/MS analysis, protein identification/ quantification, phosphopeptide enrichment and statistical analysis, are detailed in the ESI † section and previously described. 15,24 2.12.2 Pathway analysis and protein interaction networks. The initial functional evaluation was performed using the UniProt (https://www.uniprot.org) database, with a focus on protein function and relevant biological processes.…”