Author Archives: Vera

HomeMass Analytica –  Articles by: Vera

Analytical and computational workflow for in-depth analysis of oxidized complex lipids in blood plasma

Analytical and computational workflow for in-depth analysis of oxidized complex lipids in blood plasma

November 2022

Angela Criscuolo, Palina Nepachalovich, Diego Fernando Garcia-Del Rio, Mike Lange, Zhixu Ni, Massimo Baroni, Gabriele Cruciani, Laura Goracci, Matthias Blüher , Maria Fedorova

 

Abstract

Lipids are a structurally diverse class of biomolecules which can undergo a variety of chemical modifications. Among them, lipid (per)oxidation attracts most of the attention due to its significance in the regulation of inflammation, cell proliferation and death programs. Despite their apparent regulatory significance, the molecular repertoire of oxidized lipids remains largely elusive as accurate annotation of lipid modifications is complicated by their low abundance and often unknown, biological context-dependent structural diversity. Here, we provide a workflow based on the combination of bioinformatics and LC-MS/MS technologies to support identification and relative quantification of oxidized complex lipids in a modification type- and position-specific manner. The developed methodology is used to identify epilipidomics signatures of lean and obese individuals with and without type 2 diabetes. The characteristic signature of lipid modifications in lean individuals, dominated by the presence of modified octadecanoid acyl chains in phospho- and neutral lipids, is drastically shifted towards lipid peroxidation-driven accumulation of oxidized eicosanoids, suggesting significant alteration of endocrine signalling by oxidized lipids in metabolic disorders.

 

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Retinoic acid-induced 1 gene haploinsufficiency alters lipid metabolism and causes autophagy defects in Smith-Magenis syndrome

Retinoic acid-induced 1 gene haploinsufficiency alters lipid metabolism and causes autophagy defects in Smith-Magenis syndrome

November 2022

Elisa Maria Turco, Angela Maria Giada Giovenale, Laura Sireno, Martina Mazzoni, Alessandra Cammareri, Caterina Marchioretti, Laura Goracci, Alessandra Di Veroli, Elena Marchesan, Daniel D’Andrea, Antonella Falconieri, Barbara Torres, Laura Bernardini, Maria Chiara Magnifico, Alessio Paone, Serena Rinaldo, Matteo Della Monica, Stefano D’Arrigo, Diana Postorivo, Anna Maria Nardone, Giuseppe Zampino, Roberta Onesimo, Chiara Leoni, Federico Caicci, Domenico Raimondo, Elena Binda, Laura Trobiani, Antonella De Jaco, Ada Maria Tata, Daniela Ferrari, Francesca Cutruzzolà, Gianluigi Mazzoccoli, Elena Ziviani, Maria Pennuto, Angelo Luigi Vescovi, Jessica Rosati 

 

Abstract

Smith-Magenis syndrome (SMS) is a neurodevelopmental disorder characterized by cognitive and behavioral symptoms, obesity, and sleep disturbance, and no therapy has been developed to alleviate its symptoms or delay disease onset. SMS occurs due to haploinsufficiency of the retinoic acid-induced-1 (RAI1) gene caused by either chromosomal deletion (SMS-del) or RAI1 missense/nonsense mutation. The molecular mechanisms underlying SMS are unknown. Here, we generated and characterized primary cells derived from four SMS patients (two with SMS-del and two carrying RAI1 point mutations) and four control subjects to investigate the pathogenetic processes underlying SMS. By combining transcriptomic and lipidomic analyses, we found altered expression of lipid and lysosomal genes, deregulation of lipid metabolism, accumulation of lipid droplets, and blocked autophagic flux. We also found that SMS cells exhibited increased cell death associated with the mitochondrial pathology and the production of reactive oxygen species. Treatment with N-acetylcysteine reduced cell death and lipid accumulation, which suggests a causative link between metabolic dyshomeostasis and cell viability. Our results highlight the pathological processes in human SMS cells involving lipid metabolism, autophagy defects and mitochondrial dysfunction and suggest new potential therapeutic targets for patient treatment.

 

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Guiding the choice of informatics software and tools for lipidomics research applications

Guiding the choice of informatics software and tools for lipidomics research applications

February 2023.

Zhixu Ni , Michele Wölk, Geoff Jukes, Karla Mendivelso Espinosa, Robert Ahrends, Lucila Aimo, Jorge Alvarez-Jarreta, Simon Andrews, Robert Andrews, Alan Bridge, Geremy C Clair, Matthew J Conroy, Eoin Fahy, Caroline Gaud, Laura Goracci, Jürgen Hartler, Nils Hoffmann, Dominik Kopczyinki, Ansgar Korf, Andrea F Lopez-Clavijo, Adnan Malik, Jacobo Miranda Ackerman, Martijn R Molenaar, Claire O’Donovan, Tomáš Pluskal, Andrej Shevchenko, Denise Slenter, Gary Siuzdak, Martina Kutmon, Hiroshi Tsugawa, Egon L Willighagen, Jianguo Xia, Valerie B O’Donnell, Maria Fedorova

 

Abstract

Progress in mass spectrometry lipidomics has led to a rapid proliferation of studies across biology and biomedicine. These generate extremely large raw datasets requiring sophisticated solutions to support automated data processing. To address this, numerous software tools have been developed and tailored for specific tasks. However, for researchers, deciding which approach best suits their application relies on ad hoc testing, which is inefficient and time consuming. Here we first review the data processing pipeline, summarizing the scope of available tools. Next, to support researchers, LIPID MAPS provides an interactive online portal listing open-access tools with a graphical user interface. This guides users towards appropriate solutions within major areas in data processing, including (1) lipid-oriented databases, (2) mass spectrometry data repositories, (3) analysis of targeted lipidomics datasets, (4) lipid identification and (5) quantification from untargeted lipidomics datasets, (6) statistical analysis and visualization, and (7) data integration solutions. Detailed descriptions of functions and requirements are provided to guide customized data analysis workflows.

 

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A platelet lipidomics signature in patients with COVID-19

A platelet lipidomics signature in patients with COVID-19

December 2023.

Laura Goracci, Eleonora Petito, Alessandra Di Veroli, Emanuela Falcinelli, Caterina Bencivenga, Elisa Giglio, Cecilia Becattini, Edoardo De Robertis, Gaetano Vaudo, Paolo Gresele

Abstract

Ischemic cardiovascular and venous thromboembolic events are a frequent cause of death in severe COVID-19 patients. Platelet activation plays a key role in these complications, however platelet lipidomics have not been studied yet. The aim of our pilot investigation was to perform a preliminary study of platelet lipidomics in COVID-19 patients compared to healthy subjects. Lipid extraction and identification of ultrapurified platelets from eight hospitalized COVID-19 patients and eight age- and sex-matched healthy controls showed a lipidomic pattern almost completely separating COVID-19 patients from healthy controls. In particular, a significant decrease of ether phospholipids and increased levels of ganglioside GM3 were observed in platelets from COVID-19 patients. In conclusion, our study shows for the first time that platelets from COVID-19 patients display a different lipidomics signature distinguishing them from healthy controls, and suggests that altered platelet lipid metabolism may play a role in viral spreading and in the thrombotic complications of COVID-19.

Keywords: COVID-19; Platelet lipidomics.

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