MEMBRANE LIPIDOMICS AND LIPID BIOMARKERS OF RADICAL STRESS

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Free radicals react with unsaturated lipids causing chemical transformations that can act in a dual role: as signal or as damage, leading to different cellular responses. The conservation of cis geometry in the lipid double bonds has a crucial significance for cell membrane properties and functions. We discovered that, together with the previously known peroxidation process, lipid isomerization can occur endogenously due to free radical stress from sulfur-centered radicals. Cellular stress modifies the lipid structures and the process of membrane remodeling (Lands’s cycle), which affect membrane homeostasis. It is therefore vital to take a holistic approach to cellular stress, combining free-radical reactivity theory with practical analytical and biological methodologies that use lipidomics and lipid biomarkers to follow and understand the complex sequence of events in this process.
Our studies focus on the bilayer membrane as the main biological structure involved in signal transduction and adaptation, through its rapid reorganization and turnover. This research also leads into market innovation, in the key fields of biomarker discovery and nutraceuticals.

Our strategy then is a coordinated investigation of the following: 

  • The chemical reactivity of free radicals with biological membranes;

  • The use of in vitro and in vivo models to study the lipid-remodeling effects of stress, environmental and dietary conditions;

  • Fabrication and membrane-interaction studies of customized liposomal nanoparticle and nanocontainer delivery vehicles (partners of ClickGene);

  • Membrane lipidomics for evidence-based nutraceutical formulations for various health conditions (partner of E! 7348-LIPIDOMEL);

  • Endogenous formation and roles in life sciences of trans fatty acids: their mechanisms of formation, identification of the isomerizing species and their rates of reaction and diffusion, use as biomarkers of free radical stress, for evaluation of stress response in various conditions;

  • Endogenous protection of the cis lipid geometry: role and mechanisms of enzymatic and molecular defenses;

  • Developing molecular libraries for recognition of trans lipids in biological samples and nutraceuticals;

  • Effects of antitumoral drugs in membrane lipid remodeling and transformations.

 

Review:

Lipid geometrical isomerism: from chemistry to biology and diagnostics
Chatgilialoglu, C.; Ferreri, C.; Melchiorre, M.; Sansone, A.; Torreggiani, A. Chem. Rev. 2014114, 255–284. 

Editorials:

Fatty Acid-based Membrane Lipidomics: Why, What and When
Chatgilialoglu, C.; Ferreri, C.
J. Glycomics Lipidomics 20187, 1000e127.

Recent Publications:

[Cu(TPMA)(Phen)](ClO4)2: Metallodrug Nanocontainer Delivery and Membrane Lipidomics of a Neuroblastoma Cell Line Coupled with a Liposome Biomimetic Model Focusing on Fatty Acid Reactivity.
Toniolo, G.; Louka, M.; Menounou, G.; Fantoni, N.Z.; Mitrikas, G.; Efthimiadou, E.K.; Masi, A.; Bortolotti, M.; Polito, L.; Bolognesi, A.; Kellett, A.; Carla Ferreri, C;, and Chatgilialoglu, C. ACS Omega. 2018, 3, pp 15952–15965.
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Trans Lipid Library: Synthesis of Docosahexaenoic Acid (DHA) Monotrans Isomers and Regioisomer Identification in DHA-Containing
Menounou G.;  Giacometti, G.;  Scanferlato, R.; Dambruoso, P.;  Sansone, A.; Tueros, I.;  Amézaga, J.; Chatgilialoglu, C.; Ferreri, C. Chem. Res. Toxicol. 201831, 191-200.

Fatty acid-based lipidomics and membrane remodelling induced by apoE3 and apoE4 in human neuroblastoma cells
Prasinou, P.: Dafnis, I.; Giacometti, G.; Ferreri, C.; Chroni, A.; Chatgilialoglu, C. Biochim. Biophys. Acta - Biomembr. 20171859, 1967–1973. 
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