Biology subjects

Corrales, F.

Publications and source records attributed to Corrales, F..

4 recordsLinked to original sources

bioRxiv2024

Time-based quantitative proteomic and phosphoproteomic analysis of A549-ACE2 cells during SARS-CoV-2 infection

The outbreak of COVID-19, a disease caused by severe acute respiratory syndrome coronavirus 2, led to an ongoing pandemic with devastating consequences for the global economy and human health. With the global spread of SARS-CoV-2, multidisciplinary initiatives were launched to explore new diagnostic, therapeutic, and vaccination strategies. From this perspective, proteomics could help to understand the mechanisms associated with SARS-CoV-2 infection and to identify new therapeutic targets for antiviral drug repurposing and/or discovery. A TMT-based quantitative proteomics and phosphoproteomics analysis was performed to study the proteome remodeling of human lung alveolar cells transduced to express human ACE2 (A549-ACE2) after infection with SARS-CoV-2. Targeted PRM analysis was performed to assess the detectability in serum and prognostic value of selected proteins. A total of 6802 proteins and 6428 phospho-sites were identified in A549-ACE2 cells after infection with SARS-CoV-2. Regarding the viral proteome, 8 proteins were differentially expressed after 6 h of infection and reached a steady state after 9 h. In addition, we detected several phosphorylation sites of SARS-CoV-2 proteins, including two novel phosphorylation events at S410 and S416 of the viral nucleoprotein. ImportanceThe differential proteins here identified revealed that A549-ACE2 cells undergo a time-dependent regulation of essential processes, delineating the precise intervention of the cellular machinery by the viral proteins. From this mechanistic background and by applying machine learning modelling, 29 differential proteins were selected and detected in the serum of COVID-19 patients, 14 of which showed promising prognostic capacity. Targeting these proteins and the protein kinases responsible for the reported phosphorylation changes may provide efficient alternative strategies for the clinical management of COVID-19.

biochemistry↗

bioRxiv2023

SARS-CoV-2 accessory proteins involvement in inflammatory and profibrotic processes through IL11 signaling

SARS-CoV-2, the cause of the COVID19 pandemic, possesses eleven accessory proteins encoded in its genome. Their roles during infection are still not completely understood. Transcriptomic analysis revealed that both WNT5A and IL11 were significantly up-regulated in A549 cells expressing individual accessory proteins ORF6, ORF8, ORF9b or ORF9c from SARS-CoV-2 (Wuhan-Hu-1 isolate). IL11 signaling-related genes were also differentially expressed. Bioinformatics analysis disclosed that both WNT5A and IL11 were involved in pulmonary fibrosis idiopathic disease. Functional assays confirmed their association with profibrotic cell responses. Subsequently, data comparison with lung cell lines infected with SARS-CoV-2 or lung biopsies from patients with COVID19 evidenced altered gene expression that matched those obtained in this study. Our results show ORF6, ORF8, ORF9b and ORF9c involvement in inflammatory and profibrotic responses. Thus, these accessory proteins could be targeted by new therapies against COVID19 disease. Research topic(s)Viral diseases, COVID19 insights

immunology↗

bioRxiv2022

Growth hormone remodels the 3D-structure of the mitochondria of inflammatory macrophages and promotes metabolic reprogramming

Macrophages are a heterogeneous population of innate immune cells that support tissue homeostasis through their involvement in tissue development and repair, and pathogen defense. Emerging data reveal that metabolism may control macrophage polarization and function and, conversely, phenotypic polarization may drive metabolic reprogramming. Here, using biochemical analysis, correlative cryogenic fluorescence microscopy and cryo-focused ion-beam scanning electron microscopy, we demonstrate that growth hormone (GH) functions as a metabolic modulator to reprogram inflammatory GM-CSF-primed monocyte-derived macrophages (GM-MO). We found that exogenous treatment of GM-MO with recombinant human GH suppressed glycolysis, lactate production and non-mitochondrial respiration, and enhanced mitochondrial oxidative phosphorylation. Likewise, GH treatment augmented mitochondrial volume and altered mitochondrial dynamics, including the remodeling of the inner membrane to increase the density of cristae. Our data demonstrate that GH likely serves a modulatory role in the metabolism of inflammatory macrophages and suggest that metabolic reprogramming of macrophages should be considered a new target to intervene in multiple inflammatory diseases.

immunology↗

bioRxiv2019

Human Proteome Project Mass Spectrometry Data Interpretation Guidelines 3.0

The Human Proteome Organizations (HUPO) Human Proteome Project (HPP) developed Mass Spectrometry (MS) Data Interpretation Guidelines that have been applied since 2016. These guidelines have helped ensure that the emerging draft of the complete human proteome is highly accurate and with low numbers of false-positive protein identifications. Here, we describe an update to these guidelines based on consensus-reaching discussions with the wider HPP community over the past year. The revised 3.0 guidelines address several major and minor identified gaps. We have added guidelines for emerging data independent acquisition (DIA) MS workflows and for use of the new Universal Spectrum Identifier (USI) system being developed by the HUPO Proteomics Standards Initiative (PSI). In addition, we discuss updates to the standard HPP pipeline for collecting MS evidence for all proteins in the HPP, including refinements to minimum evidence. We present a new plan for incorporating MassIVE-KB into the HPP pipeline for the next (HPP 2020) cycle in order to obtain more comprehensive coverage of public MS data sets. The main checklist has been reorganized under headings and subitems and related guidelines have been grouped. In sum, Version 2.1 of the HPP MS Data Interpretation Guidelines has served well and this timely update to version 3.0 will aid the HPP as it approaches its goal of collecting and curating MS evidence of translation and expression for all predicted [~]20,000 human proteins encoded by the human genome.\n\n\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=134 SRC=\"FIGDIR/small/733576v2_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (18K):\norg.highwire.dtl.DTLVardef@8765f2org.highwire.dtl.DTLVardef@136235aorg.highwire.dtl.DTLVardef@14aef76org.highwire.dtl.DTLVardef@af33d2_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioinformatics↗