453 results on '"Chryssostomos Chatgilialoglu"'
Search Results
2. Insights from multi-omic modeling of neurodegeneration in xeroderma pigmentosum using an induced pluripotent stem cell system
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Cherif Badja, Sophie Momen, Gene Ching Chiek Koh, Soraya Boushaki, Theodoros I. Roumeliotis, Zuza Kozik, Ian Jones, Vicky Bousgouni, João M.L. Dias, Marios G. Krokidis, Jamie Young, Hongwei Chen, Ming Yang, France Docquier, Yasin Memari, Lorea Valcarcel-Zimenez, Komal Gupta, Li Ren Kong, Heather Fawcett, Florian Robert, Salome Zhao, Andrea Degasperi, Yogesh Kumar, Helen Davies, Rebecca Harris, Christian Frezza, Chryssostomos Chatgilialoglu, Robert Sarkany, Alan Lehmann, Chris Bakal, Jyoti Choudhary, Hiva Fassihi, and Serena Nik-Zainal
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CP: Neuroscience ,CP: Cell biology ,Biology (General) ,QH301-705.5 - Abstract
Summary: Xeroderma pigmentosum (XP) is caused by defective nucleotide excision repair of DNA damage. This results in hypersensitivity to ultraviolet light and increased skin cancer risk, as sunlight-induced photoproducts remain unrepaired. However, many XP patients also display early-onset neurodegeneration, which leads to premature death. The mechanism of neurodegeneration is unknown. Here, we investigate XP neurodegeneration using pluripotent stem cells derived from XP patients and healthy relatives, performing functional multi-omics on samples during neuronal differentiation. We show substantially increased levels of 5′,8-cyclopurine and 8-oxopurine in XP neuronal DNA secondary to marked oxidative stress. Furthermore, we find that the endoplasmic reticulum stress response is upregulated and reversal of the mutant genotype is associated with phenotypic rescue. Critically, XP neurons exhibit inappropriate downregulation of the protein clearance ubiquitin-proteasome system (UPS). Chemical enhancement of UPS activity in XP neuronal models improves phenotypes, albeit inadequately. Although more work is required, this study presents insights with intervention potential.
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- 2024
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3. Biomarkers of Oxidative and Radical Stress
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Chryssostomos Chatgilialoglu
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n/a ,Microbiology ,QR1-502 - Abstract
Reactive oxygen and nitrogen species (ROS/RNS) are generated as a result of normal intracellular metabolism [...]
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- 2024
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4. Radical Reactions in Organic Synthesis: Exploring in-, on-, and with-Water Methods
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Chryssostomos Chatgilialoglu, Sebastian Barata-Vallejo, and Thanasis Gimisis
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organic synthesis ,radical reactions ,water and aqueous media ,on-water reactions ,water coordination with Lewis acids ,photocatalysis ,Organic chemistry ,QD241-441 - Abstract
Radical reactions in water or aqueous media are important for organic synthesis, realizing high-yielding processes under non-toxic and environmentally friendly conditions. This overview includes (i) a general introduction to organic chemistry in water and aqueous media, (ii) synthetic approaches in, on, and with water as well as in heterogeneous phases, (iii) reactions of carbon-centered radicals with water (or deuterium oxide) activated through coordination with various Lewis acids, (iv) photocatalysis in water and aqueous media, and (v) synthetic applications bioinspired by naturally occurring processes. A wide range of chemical processes and synthetic strategies under different experimental conditions have been reviewed that lead to important functional group translocation and transformation reactions, leading to the preparation of complex molecules. These results reveal how water as a solvent/medium/reagent in radical chemistry has matured over the last two decades, with further discoveries anticipated in the near future.
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- 2024
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5. Hydroxyl Radical vs. One-Electron Oxidation Reactivities in an Alternating GC Double-Stranded Oligonucleotide: A New Type Electron Hole Stabilization
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Annalisa Masi, Amedeo Capobianco, Krzysztof Bobrowski, Andrea Peluso, and Chryssostomos Chatgilialoglu
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DNA damage ,oligonucleotide ,hydroxyl radical ,one-electron oxidation ,electron hole stabilization ,pulse radiolysis ,Microbiology ,QR1-502 - Abstract
We examined the reaction of hydroxyl radicals (HO•) and sulfate radical anions (SO4•−), which is generated by ionizing radiation in aqueous solutions under anoxic conditions, with an alternating GC doubled-stranded oligodeoxynucleotide (ds-ODN), i.e., the palindromic 5′-d(GCGCGC)-3′. In particular, the optical spectra of the intermediate species and associated kinetic data in the range of ns to ms were obtained via pulse radiolysis. Computational studies by means of density functional theory (DFT) for structural and time-dependent DFT for spectroscopic features were performed on 5′-d(GCGC)-3′. Comprehensively, our results suggest the addition of HO• to the G:C pair moiety, affording the [8-HO-G:C]• detectable adduct. The previous reported spectra of one-electron oxidation of a variety of ds-ODN were assigned to [G(-H+):C]• after deprotonation. Regarding 5′-d(GCGCGC)-3′ ds-ODN, the spectrum at 800 ns has a completely different spectral shape and kinetic behavior. By means of calculations, we assigned the species to [G:C/C:G]•+, in which the electron hole is predicted to be delocalized on the two stacked base pairs. This transient species was further hydrated to afford the [8-HO-G:C]• detectable adduct. These remarkable findings suggest that the double-stranded alternating GC sequences allow for a new type of electron hole stabilization via delocalization over the whole sequence or part of it.
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- 2023
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6. Targeted and untargeted metabolomic approach for GDM diagnosis
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Izabela Burzynska-Pedziwiatr, Danuta Dudzik, Anna Sansone, Beata Malachowska, Andrzej Zieleniak, Monika Zurawska-Klis, Carla Ferreri, Chryssostomos Chatgilialoglu, Katarzyna Cypryk, Lucyna A. Wozniak, Michal J. Markuszewski, and Malgorzata Bukowiecka-Matusiak
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GDM ,lipidomic profiling ,cholesteryl esters ,untargeted metabolomics ,biomarkers ,Biology (General) ,QH301-705.5 - Abstract
Gestational diabetes mellitus (GDM) is a disorder which manifests itself for the first time during pregnancy and is mainly connected with glucose metabolism. It is also known that fatty acid profile changes in erythrocyte membranes and plasma could be associated with obesity and insulin resistance. These factors can lead to the development of diabetes. In the reported study, we applied the untargeted analysis of plasma in GDM against standard glucose-tolerant (NGT) women to identify the differences in metabolomic profiles between those groups. We found higher levels of 2-hydroxybutyric and 3-hydroxybutyric acids. Both secondary metabolites are associated with impaired glucose metabolism. However, they are products of different metabolic pathways. Additionally, we applied lipidomic profiling using gas chromatography to examine the fatty acid composition of cholesteryl esters in the plasma of GDM patients. Among the 14 measured fatty acids characterizing the representative plasma lipidomic cluster, myristic, oleic, arachidonic, and α-linoleic acids revealed statistically significant changes. Concentrations of both myristic acid, one of the saturated fatty acids (SFAs), and oleic acid, which belong to monounsaturated fatty acids (MUFAs), tend to decrease in GDM patients. In the case of polyunsaturated fatty acids (PUFAs), some of them tend to increase (e.g., arachidonic), and some of them tend to decrease (e.g., α-linolenic). Based on our results, we postulate the importance of hydroxybutyric acid derivatives, cholesteryl ester composition, and the oleic acid diminution in the pathophysiology of GDM. There are some evidence suggests that the oleic acid can have the protective role in diabetes onset. However, metabolic alterations that lead to the onset of GDM are complex; therefore, further studies are needed to confirm our observations.
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- 2023
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7. Plasmalogens: Free Radical Reactivity and Identification of Trans Isomers Relevant to Biological Membranes
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Carla Ferreri, Alessandra Ferocino, Gessica Batani, Chryssostomos Chatgilialoglu, Vanda Randi, Maria Vittoria Riontino, Fabrizio Vetica, and Anna Sansone
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fatty acids ,cis-trans isomerization ,free radicals ,trans plasmalogens ,erythrocyte membrane ,plasmalogen analysis ,Microbiology ,QR1-502 - Abstract
Plasmalogens are membrane phospholipids with two fatty acid hydrocarbon chains linked to L-glycerol, one containing a characteristic cis-vinyl ether function and the other one being a polyunsaturated fatty acid (PUFA) residue linked through an acyl function. All double bonds in these structures display the cis geometrical configuration due to desaturase enzymatic activity and they are known to be involved in the peroxidation process, whereas the reactivity through cis-trans double bond isomerization has not yet been identified. Using 1-(1Z-octadecenyl)-2-arachidonoyl-sn-glycero-3-phosphocholine (C18 plasm-20:4 PC) as a representative molecule, we showed that the cis-trans isomerization can occur at both plasmalogen unsaturated moieties, and the product has characteristic analytical signatures useful for omics applications. Using plasmalogen-containing liposomes and red blood cell (RBC) ghosts under biomimetic Fenton-like conditions, in the presence or absence of thiols, peroxidation, and isomerization processes were found to occur with different reaction outcomes due to the particular liposome compositions. These results allow gaining a full scenario of plasmalogen reactivity under free radical conditions. Moreover, clarification of the plasmalogen reactivity under acidic and alkaline conditions was carried out, identifying the best protocol for RBC membrane fatty acid analysis due to their plasmalogen content of 15–20%. These results are important for lipidomic applications and for achieving a full scenario of radical stress in living organisms.
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- 2023
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8. Erythrocyte Plasma Membrane Lipid Composition Mirrors That of Neurons and Glial Cells in Murine Experimental In Vitro and In Vivo Inflammation
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Agnese Stanzani, Anna Sansone, Cinzia Brenna, Vito Antonio Baldassarro, Giuseppe Alastra, Luca Lorenzini, Chryssostomos Chatgilialoglu, Ilaria Laface, Carla Ferreri, Luca Maria Neri, and Laura Calzà
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lipids ,fatty acids ,cholesterol ,GM1 ,lipid rafts ,experimental allergic encephalomyelitis ,Cytology ,QH573-671 - Abstract
Lipid membrane turnover and myelin repair play a central role in diseases and lesions of the central nervous system (CNS). The aim of the present study was to analyze lipid composition changes due to inflammatory conditions. We measured the fatty acid (FA) composition in erythrocytes (RBCs) and spinal cord tissue (gas chromatography) derived from mice affected by experimental allergic encephalomyelitis (EAE) in acute and remission phases; cholesterol membrane content (Filipin) and GM1 membrane assembly (CT-B) in EAE mouse RBCs, and in cultured neurons, oligodendroglial cells and macrophages exposed to inflammatory challenges. During the EAE acute phase, the RBC membrane showed a reduction in polyunsaturated FAs (PUFAs) and an increase in saturated FAs (SFAs) and the omega-6/omega-3 ratios, followed by a restoration to control levels in the remission phase in parallel with an increase in monounsaturated fatty acid residues. A decrease in PUFAs was also shown in the spinal cord. CT-B staining decreased and Filipin staining increased in RBCs during acute EAE, as well as in cultured macrophages, neurons and oligodendrocyte precursor cells exposed to inflammatory challenges. This regulation in lipid content suggests an increased cell membrane rigidity during the inflammatory phase of EAE and supports the investigation of peripheral cell membrane lipids as possible biomarkers for CNS lipid membrane concentration and assembly.
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- 2023
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9. Assessing the Formation of Purine Lesions in Mitochondrial DNA of Cockayne Syndrome Cells
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Chryssostomos Chatgilialoglu, Marios G. Krokidis, Annalisa Masi, Sebastian Barata-Vallejo, Carla Ferreri, Barbara Pascucci, and Mariarosaria D’Errico
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mitochondrial and nuclear DNA damage ,5′,8–cyclopurines ,8–oxo–dG ,gamma radiolysis ,hydroxyl radical ,isotope dilution LC–MS/MS ,Microbiology ,QR1-502 - Abstract
Mitochondrial (mt) DNA and nuclear (n) DNA have known structures and roles in cells; however, they are rarely compared under specific conditions such as oxidative or degenerative environments that can create damage to the DNA base moieties. Six purine lesions were ascertained in the mtDNA of wild type (wt) CSA (CS3BE–wtCSA) and wtCSB (CS1AN–wtCSB) cells and defective counterparts CS3BE and CS1AN in comparison with the corresponding total (t) DNA (t = n + mt). In particular, the four 5′,8–cyclopurine (cPu) and the two 8–oxo–purine (8–oxo–Pu) lesions were accurately quantified by LC–MS/MS analysis using isotopomeric internal standards after an enzymatic digestion procedure. The 8–oxo–Pu levels were found to be in the range of 25–50 lesions/107 nucleotides in both the mtDNA and tDNA. The four cPu were undetectable in the mtDNA both in defective cells and in the wt counterparts (CSA and CSB), contrary to their detection in tDNA, indicating a nonappearance of hydroxyl radical (HO•) reactivity within the mtDNA. In order to assess the HO• reactivity towards purine nucleobases in the two genetic materials, we performed γ–radiolysis experiments coupled with the 8–oxo–Pu and cPu quantifications on isolated mtDNA and tDNA from wtCSB cells. In the latter experiments, all six purine lesions were detected in both of the DNA, showing a higher resistance to HO• attack in the case of mtDNA compared with tDNA, likely due to their different DNA helical topology influencing the relative abundance of the lesions.
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- 2022
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10. Melon juice concentrate supplementation in an animal model of obesity: Involvement of relaxin and fatty acid pathways
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Julie Carillon, Marion Saby, Sandy Barial, Anna Sansone, Roberta Scanferlato, Nathalie Gayrard, Anne-Dominique Lajoix, Bernard Jover, Chryssostomos Chatgilialoglu, and Carla Ferreri
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Superoxide dismutase ,Adipose tissue ,Membrane lipidome ,Inflammatory mediators ,Fibrosis ,Lipid remodeling ,Nutrition. Foods and food supply ,TX341-641 - Abstract
Chronic low-grade inflammation and oxidative stress associated with obesity induce molecular changes in extracellular matrix connected to relaxin pathway and fibrosis, the lipidome of various tissues and the level of lipid mediators. Increase of desaturase enzymatic activity and activation of the inflammatory mediator cascades are known to be associated with obesity. Decrease of enzymatic antioxidant defenses is strictly involved. The effects of a 10 days supplementation of encapsulated melon juice concentrate rich in superoxide dismutase were studied in Zucker Fat rats compared with Zucker Lean rats, following relaxin pathways, lipid mediators and fatty acid-based lipidomic analysis in adipose tissue and erythrocytes. Significant ameliorations in obese rats concerned the restored relaxin levels, connected with fibrosis reduction, the reduction of inflammatory mediators and a favorable fatty acid remodeling, with the decrease of unsaturated fatty acids in the lipidome of adipose tissue and erythrocytes becoming closer to the lipidome of normal rats.
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- 2019
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11. Effects of Aging and Disease Conditions in Brain of Tumor-Bearing Mice: Evaluation of Purine DNA Damages and Fatty Acid Pool Changes
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Marios G. Krokidis, Paraskevi Prasinou, Eleni K. Efthimiadou, Andrea Boari, Carla Ferreri, and Chryssostomos Chatgilialoglu
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tumor-bearing mice ,aging ,hydroxyl radical ,oxidatively-induced DNA lesions ,brain fatty acids ,age-induced remodeling ,Microbiology ,QR1-502 - Abstract
The consequences of aging and disease conditions in tissues involve reactive oxygen species (ROS) and related molecular alterations of different cellular compartments. We compared a murine model of immunodeficient (SCID) xenografted young (4 weeks old) and old (17 weeks old) mice with corresponding controls without tumor implantation and carried out a compositional evaluation of brain tissue for changes in parallel DNA and lipids compartments. DNA damage was measured by four purine 5′,8-cyclo-2′-deoxynucleosides, 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxo-dG), and 8-oxo-7,8-dihydro-2′-deoxyadenosine (8-oxo-dA). In brain lipids, the twelve most representative fatty acid levels, which were mostly obtained from the transformation of glycerophospholipids, were followed up during the aging and disease progressions. The progressive DNA damage due to age and tumoral conditions was confirmed by raised levels of 5′S-cdG and 5′S-cdA. In the brain, the remodeling involved a diminution of palmitic acid accompanied by an increase in arachidonic acid, along both age and tumor progressions, causing increases in the unsaturation index, the peroxidation index, and total TFA as indicators of increased oxidative and free radical reactivity. Our results contribute to the ongoing debate on the central role of DNA and genome instability in the aging process, and on the need for a holistic vision, which implies choosing the best biomarkers for such monitoring. Furthermore, our data highlight brain tissue for its lipid remodeling response and inflammatory signaling, which seem to prevail over the effects of DNA damage.
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- 2022
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12. Effects of Oxygen Tension for Membrane Lipidome Remodeling of Cockayne Syndrome Cell Models
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Carla Ferreri, Anna Sansone, Marios G. Krokidis, Annalisa Masi, Barbara Pascucci, Mariarosaria D’Errico, and Chryssostomos Chatgilialoglu
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CSA ,CSB ,oxygen concentration ,membrane fatty acids ,monounsaturated fatty acids ,polyunsaturated fatty acids ,Cytology ,QH573-671 - Abstract
Oxygen is important for lipid metabolism, being involved in both enzymatic transformations and oxidative reactivity, and is particularly influent when genetic diseases impair the repair machinery of the cells, such as described for Cockayne syndrome (CS). We used two cellular models of transformed fibroblasts defective for CSA and CSB genes and their normal counterparts, grown for 24 h under various oxygen tensions (hyperoxic 21%, physioxic 5% and hypoxic 1%) to examine the fatty acid-based membrane remodeling by GC analysis of fatty acid methyl esters derived from membrane phospholipids. Overall, we first distinguished differences due to oxygen tensions: (a) hyperoxia induced a general boost of desaturase enzymatic activity in both normal and defective CSA and CSB cell lines, increasing monounsaturated fatty acids (MUFA), whereas polyunsaturated fatty acids (PUFA) did not undergo oxidative consumption; (b) hypoxia slowed down desaturase activities, mostly in CSA cell lines and defective CSB, causing saturated fatty acids (SFA) to increase, whereas PUFA levels diminished, suggesting their involvement in hypoxia-related signaling. CSB-deprived cells are the most sensitive to oxidation and CSA-deprived cells are the most sensitive to the radical-based formation of trans fatty acids (TFA). The results point to the need to finely differentiate biological targets connected to genetic impairments and, consequently, suggest the better definition of cell protection and treatments through accurate molecular profiling that includes membrane lipidomes.
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- 2022
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13. Biomimetic Radical Chemistry and Applications
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Chryssostomos Chatgilialoglu
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n/a ,Organic chemistry ,QD241-441 - Abstract
Some of the most interesting aspects of free radical chemistry that emerged in the last two decades are radical enzyme mechanisms, cell signaling cascades, antioxidant activities, and free radical-induced damage of biomolecules. In addition, identification of modified biomolecules opened the way for the evaluation of in vivo damage through biomarkers. When studying free radical-based chemical mechanisms, it is very important to establish biomimetic models, which allow the experiments to be performed in a simplified environment, but suitably designed to be in strict connection with cellular conditions. The 28 papers (11 reviews and 17 articles) published in the two Special Issues of Molecules on “Biomimetic Radical Chemistry and Applications (2019 and 2021)” show a remarkable range of research in this area. The biomimetic approach is presented with new insights and reviews of the current knowledge in the field of radical-based processes relevant to health, such as biomolecular damages and repair, signaling and biomarkers, biotechnological applications, and novel synthetic approaches.
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- 2022
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14. The Erythrocyte Membrane Lipidome of Healthy Dogs: Creating a Benchmark of Fatty Acid Distribution and Interval Values
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Paraskevi Prasinou, Paolo E. Crisi, Chryssostomos Chatgilialoglu, Morena Di Tommaso, Anna Sansone, Alessandro Gramenzi, Benedetta Belà, Francesca De Santis, Andrea Boari, and Carla Ferreri
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membrane fatty acid ,lipidomic profiles ,red blood cell lipidome ,healthy dog membrane profile ,fatty acids cluster ,Veterinary medicine ,SF600-1100 - Abstract
Molecular-based approaches are rapidly developing in medicine for the evaluation of physiological and pathological conditions and discovery of new biomarkers in prevention and therapy. Fatty acid diversity and roles in health and disease in humans are topical subjects of lipidomics. In particular, membrane fatty acid-based lipidomics provides molecular data of relevance in the study of human chronic diseases, connecting metabolic, and nutritional aspects to health conditions. In veterinary medicine, membrane lipidomics, and fatty acid profiles have not been developed yet in nutritional approaches to health and in disease conditions. Using a protocol widely tested in human profiling, in the present study erythrocyte membrane lipidome was examined in 68 clinically healthy dogs, with different ages, sex, and sizes. In particular, a cluster composed of 10 fatty acids, present in membrane glycerophospholipids and representative of structural and functional properties of cell membrane, was chosen, and quantitatively analyzed. The interval values and distribution for each fatty acid of the cluster were determined, providing the first panel describing the healthy dog lipidomic membrane profile, with interesting correlation to bodyweight increases. This molecular information can be advantageously developed as benchmark in veterinary medicine for the evaluation of metabolic and nutritional status in healthy and diseased dogs.
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- 2020
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15. Increased levels of 5′,8-Cyclopurine DNA lesions in inflammatory bowel diseases
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Annalisa Masi, Paola Fortini, Marios G. Krokidis, Erminia Francesca Romeo, Cinzia Bascietto, Paola De Angelis, Valeria Guglielmi, and Chryssostomos Chatgilialoglu
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Reactive oxygen species ,Free radicals ,DNA damage ,Cyclopurines ,Inflammatory bowel diseases ,Obesity ,Medicine (General) ,R5-920 ,Biology (General) ,QH301-705.5 - Abstract
Chronic inflammation is estimated to be a causative factor in a variety of diseases. Under inflammatory conditions reactive oxygen species (ROS) and nitrogen species (RNS) are released leading to DNA damage accumulation and genomic instability. Purine 5′,8-cyclo-2′-deoxynucleosides (cPu) are oxidative DNA lesions, exclusively derived from the attack of HO• radicals, which are known to have cytotoxic and mutagenic properties. Herein, we have analyzed the presence of cPu in genomic DNA isolated from fresh colon and visceral adipose tissue biopsies collected from inflammatory bowel diseases (IBD)-affected patients and severely obese subjects, respectively, versus what observed in the control specimens. In colon biopsies, characterized by a higher gene expression level of inducible nitric oxide synthase (iNOS), a significant increase of 8-oxo-7,8-dihydro-2′-deoxyadenosine (8-oxo-dA) and 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxo-dG) lesions and an accumulation of both diastereomeric cPu have been detected. In contrast, the 8-oxo-dA and 8-oxo-dG levels were extremely lower compared to the colon tissues values and no accumulation of cPu, in the inflamed visceral adipose tissue biopsies isolated from bariatric patients versus the lean counterpart was reported. In addition, in adipose tissue undetectable levels of iNOS have been found. These data suggest a potential involvement of cPu in the colon cancer susceptibility observed in IBD patients.
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- 2020
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16. Sapienic Acid Metabolism Influences Membrane Plasticity and Protein Signaling in Breast Cancer Cell Lines
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Ertan Küçüksayan, Anna Sansone, Chryssostomos Chatgilialoglu, Tomris Ozben, Demet Tekeli, Günel Talibova, and Carla Ferreri
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membrane fatty acids ,breast cancer ,membrane remodeling ,fatty acid supplementation ,cancer signaling activation ,membrane lipidome ,Cytology ,QH573-671 - Abstract
The importance of sapienic acid (6c-16:1), a monounsaturated fatty acid of the n-10 family formed from palmitic acid by delta-6 desaturase, and of its metabolism to 8c-18:1 and sebaleic acid (5c,8c-18:2) has been recently assessed in cancer. Data are lacking on the association between signaling cascades and exposure to sapienic acid comparing cell lines of the same cancer type. We used 50 μM sapienic acid supplementation, a non-toxic concentration, to cultivate MCF-7 and 2 triple-negative breast cancer cells (TNBC), MDA-MB-231 and BT-20. We followed up for three hours regarding membrane fatty acid remodeling by fatty acid-based membrane lipidome analysis and expression/phosphorylation of EGFR (epithelial growth factor receptor), mTOR (mammalian target of rapamycin) and AKT (protein kinase B) by Western blotting as an oncogenic signaling cascade. Results evidenced consistent differences among the three cell lines in the metabolism of n-10 fatty acids and signaling. Here, a new scenario is proposed for the role of sapienic acid: one based on changes in membrane composition and properties, and the other based on changes in expression/activation of growth factors and signaling cascades. This knowledge can indicate additional players and synergies in breast cancer cell metabolism, inspiring translational applications of tailored membrane lipid strategies to assist pharmacological interventions.
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- 2022
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17. [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
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Gianluca Toniolo, Maria Louka, Georgia Menounou, Nicolò Zuin Fantoni, George Mitrikas, Eleni K. Efthimiadou, Annalisa Masi, Massimo Bortolotti, Letizia Polito, Andrea Bolognesi, Andrew Kellett, Carla Ferreri, and Chryssostomos Chatgilialoglu
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Chemistry ,QD1-999 - Published
- 2018
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18. The Fatty Acid-Based Erythrocyte Membrane Lipidome in Dogs with Chronic Enteropathy
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Paolo Emidio Crisi, Alessia Luciani, Morena Di Tommaso, Paraskevi Prasinou, Francesca De Santis, Chryssostomos Chatgilialoglu, Marco Pietra, Fabio Procoli, Anna Sansone, Maria Veronica Giordano, Alessandro Gramenzi, Carla Ferreri, and Andrea Boari
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canine chronic enteropathy ,non-responsive enteropathy ,protein-losing enteropathy ,membrane fatty acids ,lipidomic profile ,red blood cell membrane lipidome ,Veterinary medicine ,SF600-1100 ,Zoology ,QL1-991 - Abstract
Canine chronic enteropathies (CEs) are inflammatory processes resulting from complex interplay between the mucosal immune system, intestinal microbiome, and dietary components in susceptible dogs. Fatty acids (FAs) play important roles in the regulation of physiologic and metabolic pathways and their role in inflammation seems to be dual, as they exhibit pro–inflammatory and anti–inflammatory functions. Analysis of red blood cell (RBC) membrane fatty acid profile represents a tool for assessing the quantity and quality of structural and functional molecular components. This study was aimed at comparing the FA membrane profile, determined by Gas Chromatography and relevant lipid parameter of 48 CE dogs compared with 68 healthy dogs. In CE patients, the levels of stearic (p < 0.0001), dihomo–gamma–linolenic, eicosapentaenoic (p = 0.02), and docosahexaenoic (p = 0.02) acids were significantly higher, and those of palmitic (p < 0.0001) and linoleic (p = 0.0006) acids were significantly lower. Non-responder dogs presented higher percentages of vaccenic acid (p = 0.007), compared to those of dogs that responded to diagnostic trials. These results suggest that lipidomic status may reflect the “gut health”, and the non–invasive analysis of RBC membrane might have the potential to become a candidate biomarker in the evaluation of dogs affected by CE.
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- 2021
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19. Biomimetic Ketone Reduction by Disulfide Radical Anion
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Sebastian Barata-Vallejo, Konrad Skotnicki, Carla Ferreri, Bronislaw Marciniak, Krzysztof Bobrowski, and Chryssostomos Chatgilialoglu
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biomimetic chemistry ,cysteine ,ketone reduction ,free radicals ,pulse radiolysis ,kinetics ,Organic chemistry ,QD241-441 - Abstract
The conversion of ribonucleosides to 2′-deoxyribonucleosides is catalyzed by ribonucleoside reductase enzymes in nature. One of the key steps in this complex radical mechanism is the reduction of the 3′-ketodeoxynucleotide by a pair of cysteine residues, providing the electrons via a disulfide radical anion (RSSR•−) in the active site of the enzyme. In the present study, the bioinspired conversion of ketones to corresponding alcohols was achieved by the intermediacy of disulfide radical anion of cysteine (CysSSCys)•− in water. High concentration of cysteine and pH 10.6 are necessary for high-yielding reactions. The photoinitiated radical chain reaction includes the one-electron reduction of carbonyl moiety by disulfide radical anion, protonation of the resulting ketyl radical anion by water, and H-atom abstraction from CysSH. The (CysSSCys)•− transient species generated by ionizing radiation in aqueous solutions allowed the measurement of kinetic data with ketones by pulse radiolysis. By measuring the rate of the decay of (CysSSCys)•− at λmax = 420 nm at various concentrations of ketones, we found the rate constants of three cyclic ketones to be in the range of 104–105 M−1s−1 at ~22 °C.
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- 2021
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20. The Two Faces of the Guanyl Radical: Molecular Context and Behavior
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Chryssostomos Chatgilialoglu
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guanine ,guanyl radical ,tautomerism ,guanine radical cation ,oligonucleotides ,DNA ,Organic chemistry ,QD241-441 - Abstract
The guanyl radical or neutral guanine radical G(-H)• results from the loss of a hydrogen atom (H•) or an electron/proton (e–/H+) couple from the guanine structures (G). The guanyl radical exists in two tautomeric forms. As the modes of formation of the two tautomers, their relationship and reactivity at the nucleoside level are subjects of intense research and are discussed in a holistic manner, including time-resolved spectroscopies, product studies, and relevant theoretical calculations. Particular attention is given to the one-electron oxidation of the GC pair and the complex mechanism of the deprotonation vs. hydration step of GC•+ pair. The role of the two G(-H)• tautomers in single- and double-stranded oligonucleotides and the G-quadruplex, the supramolecular arrangement that attracts interest for its biological consequences, are considered. The importance of biomarkers of guanine DNA damage is also addressed.
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- 2021
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21. Correction: Krokidis, M.G., et al. Oxygen-Dependent Accumulation of Purine DNA Lesions in Cockayne Syndrome Cells. Cells 2020, 9, 1671
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Marios G. Krokidis, Mariarosaria D’Errico, Barbara Pascucci, Eleonora Parlanti, Annalisa Masi, Carla Ferreri, and Chryssostomos Chatgilialoglu
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n/a ,Cytology ,QH573-671 - Abstract
The originally published article [...]
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- 2020
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22. Free-Radical-Mediated Formation of Trans-Cardiolipin Isomers, Analytical Approaches for Lipidomics and Consequences of the Structural Organization of Membranes
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Fabrizio Vetica, Anna Sansone, Cesare Meliota, Gessica Batani, Marinella Roberti, Chryssostomos Chatgilialoglu, and Carla Ferreri
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cardiolipin ,linoleic acid ,free radicals ,cis-trans isomerization ,γ-irradiation ,Fenton reaction ,Microbiology ,QR1-502 - Abstract
Free-radical-mediated processes, such as peroxidation, isomerization and hydrogenation affecting fatty acid integrity and biological functions, have a trans-disciplinary relevance. Cardiolipins (CL, (1,3-diphosphatidyl-sn-glycerol)) and tetra-linoleoyl-CL are complex phospholipids, exclusively present in the Inner Mitochondrial Membrane (IMM) lipids, where they maintain membrane integrity and regulate enzyme functionalities. Peroxidation pathways and fatty acid remodeling are known causes of mitochondrial disfunctions and pathologies, including cancer. Free-radical-mediated isomerization with the change of the cis CL into geometrical trans isomers is an unknown process with possible consequences on the supramolecular membrane lipid organization. Here, the formation of mono-trans CL (MT-CL) and other trans CL isomers (T-CL) is reported using CL from bovine heart mitochondria and thiyl radicals generated by UV-photolysis from 2-mercaptoethanol. Analytical approaches for CL isomer separation and identification via 1H/13C NMR are provided, together with the chemical study of CL derivatization to fatty acid methyl esters (FAME), useful for lipidomics and metabolomics research. Kinetics information of the radical chain isomerization process was obtained using γ-irradiation conditions. The CL isomerization affected the structural organization of membranes, as tested by the reduction in unilamellar liposome diameter, and accompanied the well-known process of oxidative consumption induced by Fenton reagents. These results highlight a potential new molecular modification pathway of mitochondrial lipids with wide applications to membrane functions and biological consequences.
- Published
- 2020
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23. Oxygen-Dependent Accumulation of Purine DNA Lesions in Cockayne Syndrome Cells
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Marios G. Krokidis, Mariarosaria D’Errico, Barbara Pascucci, Eleonora Parlanti, Annalisa Masi, Carla Ferreri, and Chryssostomos Chatgilialoglu
- Subjects
CSA ,CSB ,oxygen concentration ,free radicals ,oxidatively generated DNA damage ,isotope dilution LC-MS/MS ,Cytology ,QH573-671 - Abstract
Cockayne Syndrome (CS) is an autosomal recessive neurodegenerative premature aging disorder associated with defects in nucleotide excision repair (NER). Cells from CS patients, with mutations in CSA or CSB genes, present elevated levels of reactive oxygen species (ROS) and are defective in the repair of a variety of oxidatively generated DNA lesions. In this study, six purine lesions were ascertained in wild type (wt) CSA, defective CSA, wtCSB and defective CSB-transformed fibroblasts under different oxygen tensions (hyperoxic 21%, physioxic 5% and hypoxic 1%). In particular, the four 5′,8-cyclopurine (cPu) and the two 8-oxo-purine (8-oxo-Pu) lesions were accurately quantified by LC-MS/MS analysis using isotopomeric internal standards after an enzymatic digestion procedure. cPu levels were found comparable to 8-oxo-Pu in all cases (3–6 lesions/106 nucleotides), slightly increasing on going from hyperoxia to physioxia to hypoxia. Moreover, higher levels of four cPu were observed under hypoxia in both CSA and CSB-defective cells as compared to normal counterparts, along with a significant enhancement of 8-oxo-Pu. These findings revealed that exposure to different oxygen tensions induced oxidative DNA damage in CS cells, repairable by NER or base excision repair (BER) pathways. In NER-defective CS patients, these results support the hypothesis that the clinical neurological features might be connected to the accumulation of cPu. Moreover, the elimination of dysfunctional mitochondria in CS cells is associated with a reduction in the oxidative DNA damage.
- Published
- 2020
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24. Lipid profile changes in erythrocyte membranes of women with diagnosed GDM.
- Author
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Malgorzata Bukowiecka-Matusiak, Izabela Burzynska-Pedziwiatr, Anna Sansone, Beata Malachowska, Monika Zurawska-Klis, Carla Ferreri, Chryssostomos Chatgilialoglu, Tomasz Ochedalski, Katarzyna Cypryk, and Lucyna Alicja Wozniak
- Subjects
Medicine ,Science - Abstract
Gestational diabetes mellitus (GDM) is a glucose intolerance that begins or is first recognized during pregnancy. It is currently a growing health problem worldwide affecting from 1% to 14% of all pregnant women depending on racial and ethnic group as well as the diagnostic and screening criteria. Our preliminary study aimed at investigating the erythrocyte membrane fatty acid profiles of pregnant women, in particular with diagnosed with gestational diabetes mellitus (GDM), and with normal glucose tolerant (NGT) pregnant women as a control group. The study group comprised 43 pregnant women, 32 of whom were diagnosed with GDM according to the WHO criteria, and 11 with normal glucose tolerance. The erythrocyte membrane phospholipids were obtained according to the Folch extraction procedure. Fatty acids (FA) were analyzed by gas chromatography (GC) as the corresponding fatty acid methyl esters (FAME). A cluster of 14 fatty acids identified contained >98% of the recognized peaks in the GC analysis. The analysis of fatty acids from erythrocytes revealed important differences between GDM and NGT women in the third trimester, and the results were correlated with biochemical data. Among the 14 measured FA representing the membrane lipidomic profile, the levels of three saturated FA (myristic, palmitic, stearic acids) tended to decrease in GDM patients, with the percentage content of stearic acid significantly changed. The relative content of monounsaturated fatty acids (MUFA) tended to increase, in particular the oleic acid and vaccenic acid contents were significantly increased in erythrocyte membranes of the GDM group in comparison with the NGT group. The GDM group demonstrated higher sapienic acid levels (+29%) but this change was not statistically significant. This study revealed association between an impaired cis-vaccenic acid concentration in erythrocytes membrane and GDM development. No significant changes of polyunsaturated fatty acids (PUFA) were observed in GDM and NGT erythrocytes. We postulate, basing on the differences between the GDM and NGT lipidomic profiles, that stearic and cis-vaccenic acids can be considered as dual biomarkers of specific SFA-MUFA conversion pathway, involving the coupling of delta-9 desaturase and elongase enzymes. Our results indicate that the SFA-MUFA families may be involved in the pathophysiology of metabolic diseases such as GDM, but the further studies are needed to confirm our hypothesis. In conclusion, the erythrocyte membranes of GDM women undergo remodeling resulting in abnormal fatty acid profiles, which are reflection of the long-term status of organism and can have great impact on both the mother and her offspring.
- Published
- 2018
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25. Biomimetic chemistry on the protection of cis phospholipid from the thiyl radical isomerization by common antioxidants
- Author
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Ioannis N. Lykakis, Carla Ferreri, and Chryssostomos Chatgilialoglu
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Organic chemistry ,QD241-441 - Published
- 2015
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26. Purine DNA Lesions at Different Oxygen Concentration in DNA Repair-Impaired Human Cells (EUE-siXPA)
- Author
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Marios G. Krokidis, Eleonora Parlanti, Mariarosaria D’Errico, Barbara Pascucci, Anna Pino, Alessandro Alimonti, Donatella Pietraforte, Annalisa Masi, Carla Ferreri, and Chryssostomos Chatgilialoglu
- Subjects
xpa, dna repair, hypoxia, oxidative lesions, hydroxyl radicals, oxygen concentration ,Cytology ,QH573-671 - Abstract
Xeroderma Pigmentosum (XP) is a DNA repair disease characterized by nucleotide excision repair (NER) malfunction, leading to photosensitivity and increased incidence of skin malignancies. The role of XP-A in NER pathways has been well studied while discrepancies associated with ROS levels and the role of radical species between normal and deficient XPA cell lines have been observed. Using liquid chromatography tandem mass spectrometry we have determined the four 5’,8-cyclopurines (cPu) lesions (i.e., 5′R-cdG, 5′S-cdG, 5′R-cdA and 5′S-cdA), 8-oxo-dA and 8-oxo-dG in wt (EUE-pBD650) and XPA-deficient (EUE-siXPA) human embryonic epithelial cell lines, under different oxygen tension (hyperoxic 21%, physioxic 5% and hypoxic 1%). The levels of Fe and Cu were also measured. The main findings of our study were: (i) the total amount of cPu (1.82−2.52 lesions/106 nucleotides) is the same order of magnitude as 8-oxo-Pu (3.10−4.11 lesions/106 nucleotides) in both cell types, (ii) the four cPu levels are similar in hyperoxic and physioxic conditions for both wt and deficient cell lines, whereas 8-oxo-Pu increases in all cases, (iii) both wt and deficient cell lines accumulated high levels of cPu under hypoxic compared to physioxic conditions, whereas the 8-oxo-Pu levels show an opposite trend, (iv) the diastereoisomeric ratios 5′R/5′S are independent of oxygen concentration being 0.29 for cdG and 2.69 for cdA for EUE-pBD650 (wt) and 0.32 for cdG and 2.94 for cdA for EUE-siXPA (deficient), (v) in deficient cell lines Fe levels were significantly higher. The data show for the first time the connection of oxygen concentration in cells with different DNA repair ability and the levels of different DNA lesions highlighting the significance of cPu. Membrane lipidomic data at 21% O2 indicated differences in the fatty acid contents between wild type and deficient cells, envisaging functional effects on membranes associated with the different repair capabilities, to be further investigated.
- Published
- 2019
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27. New Insights into the Reaction Paths of Hydroxyl Radicals with Purine Moieties in DNA and Double-Stranded Oligodeoxynucleotides
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Chryssostomos Chatgilialoglu, Marios G. Krokidis, Annalisa Masi, Sebastian Barata-Vallejo, Carla Ferreri, Michael A. Terzidis, Tomasz Szreder, and Krzysztof Bobrowski
- Subjects
dna damage ,5′,8-cyclopurines ,8-oxo-dg ,free radicals ,pulse radiolysis ,gamma radiolysis ,fenton reaction ,oligonucleotides ,Organic chemistry ,QD241-441 - Abstract
The reaction of hydroxyl radical (HO•) with DNA produces many primary reactive species and many lesions as final products. In this study, we have examined the optical spectra of intermediate species derived from the reaction of HO• with a variety of single- and double-stranded oligodeoxynucleotides and ct-DNA in the range of 1 μs to 1 ms by pulse radiolysis using an Intensified Charged Coupled Device (ICCD) camera. Moreover, we applied our published analytical protocol based on an LC-MS/MS system with isotopomeric internal standards to enable accurate and precise measurements of purine lesion formation. In particular, the simultaneous measurement of the four purine 5′,8-cyclo-2′-deoxynucleosides (cPu) and two 8-oxo-7,8-dihydro-2′-deoxypurine (8-oxo-Pu) was obtained upon reaction of genetic material with HO• radicals generated either by γ-radiolysis or Fenton-type reactions. Our results contributed to the debate in the literature regarding absolute level of lesions, method of HO• radical generation, 5′R/5′S diastereomeric ratio in cPu, and relative abundance between cPu and 8-oxo-Pu.
- Published
- 2019
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28. Converging Fate of the Oxidation and Reduction of 8-Thioguanosine
- Author
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Katarzyna Taras-Goslinska, Fabrizio Vetica, Sebastián Barata-Vallejo, Virginia Triantakostanti, Bronisław Marciniak, and Chryssostomos Chatgilialoglu
- Subjects
photolysis ,laser flash photolysis ,γ-radiolysis ,singlet oxygen ,nucleosides ,free radicals ,reaction mechanism ,Organic chemistry ,QD241-441 - Abstract
Thione-containing nucleobases have attracted the attention of the scientific community for their application in oncology, virology, and transplantology. The detailed understanding of the reactivity of the purine derivative 8-thioguanosine (8-TG) with reactive oxygen species (ROS) and free radicals is crucial for its biological relevance. An extensive investigation on the fate of 8-TG under both reductive and oxidative conditions is here reported, and it was tested by employing steady-state photooxidation, laser flash photolysis, as well as γ-radiolysis in aqueous solutions. The characterization of the 8-TG T1 excited state by laser flash photolysis and the photooxidation experiments confirmed that singlet oxygen is a crucial intermediate in the formation of the unexpected reduced product guanosine, without the formation of the usual oxygenated sulfinic or sulfonic acids. Furthermore, a thorough screening of different radiolytic conditions upon γ-radiation afforded the reduced product. These results were rationalized by performing control experiments in the predominant presence of each reactive species formed by radiolysis of water, and the mechanistic pathway scenario was postulated on these bases.
- Published
- 2019
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29. The Entrapment of Somatostatin in a Lipid Formulation: Retarded Release and Free Radical Reactivity
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Anna Vita Larocca, Gianluca Toniolo, Silvia Tortorella, Marios G. Krokidis, Georgia Menounou, Giuseppe Di Bella, Chryssostomos Chatgilialoglu, and Carla Ferreri
- Subjects
liposomal somatostatin ,retarded delivery ,free radicals ,isomerization ,trans lipid ,peroxidation ,Organic chemistry ,QD241-441 - Abstract
The natural peptide somatostatin has hormonal and cytostatic effects exerted by the binding to specific receptors in various tissues. Therapeutic uses are strongly prevented by its very short biological half-life of 1–2 min due to enzymatic hydrolysis, therefore encapsulation methodologies are explored to overcome the need for continuous infusion regimes. Multilamellar liposomes made of natural phosphatidylcholine were used for the incorporation of a mixture of somatostatin and sorbitol dissolved in citrate buffer at pH = 5. Lyophilization and reconstitution of the suspension were carried out, showing the flexibility of this preparation. Full characterization of this suspension was obtained as particle size, encapsulation efficiency and retarded release properties in aqueous medium and human plasma. Liposomal somatostatin incubated at 37 °C in the presence of Fe(II) and (III) salts were used as a biomimetic model of drug-cell membrane interaction, evidencing the free radical processes of peroxidation and isomerization that transform the unsaturated fatty acid moieties of the lipid vesicles. This study offers new insights into a liposomal delivery system and highlights molecular reactivity of sulfur-containing drugs with its carrier or biological membranes for pharmacological applications.
- Published
- 2019
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30. 5′,8-Cyclopurine Lesions in DNA Damage: Chemical, Analytical, Biological, and Diagnostic Significance
- Author
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Chryssostomos Chatgilialoglu, Carla Ferreri, Nicholas E. Geacintov, Marios G. Krokidis, Yuan Liu, Annalisa Masi, Vladimir Shafirovich, Michael A. Terzidis, and Pawlos S. Tsegay
- Subjects
reactive oxygen species ,free radicals ,DNA damage ,cyclopurines ,DNA and RNA polymerases ,nucleotide excision repair ,LC-MS/MS ,xeroderma pigmentosum ,cancer ,Cytology ,QH573-671 - Abstract
Purine 5′,8-cyclo-2′-deoxynucleosides (cPu) are tandem-type lesions observed among the DNA purine modifications and identified in mammalian cellular DNA in vivo. These lesions can be present in two diasteroisomeric forms, 5′R and 5′S, for each 2′-deoxyadenosine and 2′-deoxyguanosine moiety. They are generated exclusively by hydroxyl radical attack to 2′-deoxyribose units generating C5′ radicals, followed by cyclization with the C8 position of the purine base. This review describes the main recent achievements in the preparation of the cPu molecular library for analytical and DNA synthesis applications for the studies of the enzymatic recognition and repair mechanisms, their impact on transcription and genetic instability, quantitative determination of the levels of lesions in various types of cells and animal model systems, and relationships between the levels of lesions and human health, disease, and aging, as well as the defining of the detection limits and quantification protocols.
- Published
- 2019
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31. Assessment of DNA Topoisomerase I Unwinding Activity, Radical Scavenging Capacity, and Inhibition of Breast Cancer Cell Viability of N-alkyl-acridones and N,N′-dialkyl-9,9′-biacridylidenes
- Author
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Marios G. Krokidis, Zara Molphy, Eleni K. Efthimiadou, Marianna Kokoli, Smaragda-Maria Argyri, Irini Dousi, Annalisa Masi, Kyriakos Papadopoulos, Andrew Kellett, and Chryssostomos Chatgilialoglu
- Subjects
N,N′-dialkyl-9,9′-biacridylidenes ,topoisomerase I ,DNA intercalation ,DNA binding ,radical scavenging capacity ,cytotoxic activity ,Microbiology ,QR1-502 - Abstract
The anticancer activity of acridone derivatives has attracted increasing interest, therefore, a variety of substituted analogs belonging to this family have been developed and evaluated for their anti-cancer properties. A series of N-alkyl-acridones 1−6 and N,N′-dialkyl-9,9′-biacridylidenes 7−12 with variable alkyl chains were examined for their topoisomerase I activity at neutral and acidic conditions as well as for their binding capacity to calf thymus and possible radical trapping antioxidant activity. It was found that at a neutral pH, topoisomerase I activity of both classes of compounds was similar, while under acidic conditions, enhanced intercalation was observed. N-alkyl-acridone derivatives 1−6 exhibited stronger, dose-dependent, cytotoxic activity against MCF-7 human breast epithelial cancer cells than N,N′-dialkyl-9,9′-biacridylidenes 7−12, revealing that conjugation of the heteroaromatic system plays a significant role on the effective distribution of the compound in the intracellular environment. Cellular investigation of long alkyl derivatives against cell migration exhibited 40−50% wound healing effects and cytoplasm diffusion, while compounds with shorter alkyl chains were accumulated both in the nucleus and cytoplasm. All N,N′-dialkyl-9,9′-biacridylidenes showed unexpected high scavenging activity towards DPPH or ABTS radicals which may be explained by higher stabilization of radical cations by the extended conjugation of heteroaromatic ring system.
- Published
- 2019
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32. Diastereomeric Recognition of 5’,8-cyclo-2’-Deoxyadenosine Lesions by Human Poly(ADP-ribose) Polymerase 1 in a Biomimetic Model
- Author
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Annalisa Masi, Arianna Sabbia, Carla Ferreri, Francesco Manoli, Yanhao Lai, Eduardo Laverde, Yuan Liu, Marios G. Krokidis, Chryssostomos Chatgilialoglu, and Maria Rosaria Faraone Mennella
- Subjects
human poly(ADP-ribose) polymerase 1 (PARP1) ,PARP-DNA complex ,DNA-protein binding ,DNA repair ,5’,8-Cyclopurine-2’-deoxynucleoside ,DNA damage ,DNA repair efficiency ,Cytology ,QH573-671 - Abstract
5’,8-Cyclo-2’-deoxyadenosine (cdA), in the 5’R and 5’Sdiastereomeric forms, are typical non strand-break oxidative DNA lesions, induced by hydroxyl radicals, with emerging importance as a molecular marker. These lesions are exclusively repaired by the nucleotide excision repair (NER) mechanism with a low efficiency, thus readily accumulating in the genome. Poly(ADP-ribose) polymerase1 (PARP1) acts as an early responder to DNA damage and plays a key role as a nick sensor in the maintenance of the integrity of the genome by recognizing nicked DNA. So far, it was unknown whether the two diastereomeric cdA lesions could induce specific PARP1 binding. Here, we provide the first evidence of PARP1 to selectively recognize the diastereomeric lesions of 5’S-cdA and 5’R-cdA in vitro as compared to deoxyadenosine in model DNA substrates (23-mers) by using circular dichroism, fluorescence spectroscopy, immunoblotting analysis, and gel mobility shift assay. Several features of the recognition of the damaged and undamaged oligonucleotides by PARP1 were characterized. Remarkably, PARP1 exhibits different affinities in binding to a double strand (ds) oligonucleotide, which incorporates cdA lesions in R and S diastereomeric form. In particular, PARP1 proved to bind oligonucleotides, including a 5’S-cdA, with a higher affinity constant for the 5’S lesion in a model of ds DNA than 5’R-cdA, showing different recognition patterns, also compared with undamaged dA. This new finding highlights the ability of PARP1 to recognize and differentiate the distorted DNA backbone in a biomimetic system caused by different diastereomeric forms of a cdA lesion.
- Published
- 2019
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33. Hexadecenoic Fatty Acid Isomers in Human Blood Lipids and Their Relevance for the Interpretation of Lipidomic Profiles.
- Author
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Anna Sansone, Evanthia Tolika, Maria Louka, Valentina Sunda, Simone Deplano, Michele Melchiorre, Dimitrios Anagnostopoulos, Chryssostomos Chatgilialoglu, Cesare Formisano, Rosa Di Micco, Maria Rosaria Faraone Mennella, and Carla Ferreri
- Subjects
Medicine ,Science - Abstract
Monounsaturated fatty acids (MUFA) are emerging health biomarkers, and in particular the ratio between palmitoleic acid (9cis-16:1) and palmitic acid (16:0) affords the delta-9 desaturase index that is increased in obesity. Recently, other positional and geometrical MUFA isomers belonging to the hexadecenoic family (C16 MUFA) were found in circulating lipids, such as sapienic acid (6cis-16:1), palmitelaidic acid (9trans-16:1) and 6trans-16:1. In this work we report: i) the identification of sapienic acid as component of human erythrocyte membrane phospholipids with significant increase in morbidly obese patients (n = 50) compared with age-matched lean controls (n = 50); and ii) the first comparison of erythrocyte membrane phospholipids (PL) and plasma cholesteryl esters (CE) in morbidly obese patients highlighting that some of their fatty acid levels have opposite trends: increases of both palmitic and sapienic acids with the decrease of linoleic acid (9cis,12cis-18:2, omega-6) in red blood cell (RBC) membrane PL were reversed in plasma CE, whereas the increase of palmitoleic acid was similar in both lipid species. Consequentially, desaturase enzymatic indexes gave different results, depending on the lipid class used for the fatty acid content. The fatty acid profile of morbidly obese subjects also showed significant increases of stearic acid (C18:0) and C20 omega-6, as well as decreases of oleic acid (9cis-18:1) and docosahexaenoic acid (C22:6 omega-3) as compared with lean healthy controls. Trans monounsaturated and polyunsaturated fatty acids were also measured and found significantly increased in both lipid classes of morbidly obese subjects. These results highlight the C16 MUFA isomers as emerging metabolic marker provided that the assignment of the double bond position and geometry is correctly performed, thus identifying the corresponding lipidomic pathway. Since RBC membrane PL and plasma CE have different fatty acid trends, caution must also be used in the choice of lipid species for the interpretation of lipidomic profiles.
- Published
- 2016
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34. Recent Applications of the (TMS)3SiH Radical-Based Reagent
- Author
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Chryssostomos Chatgilialoglu and Jacques Lalevée
- Subjects
tris(trimethylsilyl)silane ,radical reactions ,silyl radical ,reduction ,hydrosilylation ,photopolymerization ,Organic chemistry ,QD241-441 - Abstract
This review article focuses on the recent applications of tris(trimethylsilyl)silane as a radical-based reagent in organic chemistry. Numerous examples of the successful use of (TMS)3SiH in radical reductions, hydrosilylation and consecutive radical reactions are given. The use of (TMS)3SiH allows reactions to be carried out under mild conditions with excellent yields of products and remarkable chemo-, regio-, and stereoselectivity. The strategic role of (TMS)3SiH in polymerization is underlined with emphasis on the photo-induced radical polymerization of olefins and photo-promoted cationic polymerization of epoxides.
- Published
- 2012
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35. Nutrition and Reproductive Health: Sperm versus Erythrocyte Lipidomic Profile and ω-3 Intake
- Author
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Gabriela Ruth Mendeluk, Mariano Isaac Cohen, Carla Ferreri, and Chryssostomos Chatgilialoglu
- Subjects
Nutritional diseases. Deficiency diseases ,RC620-627 - Abstract
Fatty acid analyses of sperm and erythrocyte cell membrane phospholipids in idiopathic infertile patients evidenced that erythrocyte contents of EPA, DHA, omega-6–omega-3 ratio and arachidonic acid provide a mathematical correspondence for the prediction of EPA level in sperm cells. The erythrocyte lipidomic profile of patients was significantly altered, with signatures of typical Western pattern dietary habits and no fish intake. A supplementation with nutritional levels of EPA and DHA and antioxidants was then performed for 3 months, with the follow-up of both erythrocyte and sperm cell membranes composition as well as conventional sperm parameters. Some significant changes were found in the lipidomic membrane profile of erythrocyte but not in sperm cells, which correspondently did not show significant parameter ameliorations. This is the first report indicating that membrane lipids of different tissues do not equally metabolize the fatty acid elements upon supplementation. Molecular diagnostic tools are necessary to understand the cell metabolic turnover and monitor the success of nutraceuticals for personalized treatments.
- Published
- 2015
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36. trans-Double Bond-Containing Liposomes as Potential Carriers for Drug Delivery
- Author
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Giorgia Giacometti, Marina Marini, Kyriakos Papadopoulos, Carla Ferreri, and Chryssostomos Chatgilialoglu
- Subjects
trans-phospholipids ,liposomes ,drug-delivery system ,trans fatty acids ,cis-trans isomerization ,Organic chemistry ,QD241-441 - Abstract
The use of liposomes has been crucial for investigations in biomimetic chemical biology as a membrane model and in medicinal chemistry for drug delivery. Liposomes are made of phospholipids whose biophysical characteristics strongly depend on the type of fatty acid moiety, where natural unsaturated lipids always have the double bond geometry in the cis configuration. The influence of lipid double bond configuration had not been considered so far with respect to the competence of liposomes in delivery. We were interested in evaluating possible changes in the molecular properties induced by the conversion of the double bond from cis to trans geometry. Here we report on the effects of the addition of trans-phospholipids supplied in different amounts to other liposome constituents (cholesterol, neutral phospholipids and cationic surfactants), on the size, ζ-potential and stability of liposomal formulations and on their ability to encapsulate two dyes such as rhodamine B and fluorescein. From a biotechnological point of view, trans-containing liposomes proved to have different characteristics from those containing the cis analogues, and to influence the incorporation and release of the dyes. These results open new perspectives in the use of the unnatural lipid geometry, for the purpose of changing liposome behavior and/or of obtaining molecular interferences, also in view of synergic effects of cell toxicity, especially in antitumoral strategies.
- Published
- 2017
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37. Fatty Acids in Membranes as Homeostatic, Metabolic and Nutritional Biomarkers: Recent Advancements in Analytics and Diagnostics
- Author
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Carla Ferreri, Annalisa Masi, Anna Sansone, Giorgia Giacometti, Anna Vita Larocca, Georgia Menounou, Roberta Scanferlato, Silvia Tortorella, Domenico Rota, Marco Conti, Simone Deplano, Maria Louka, Anna Rosaria Maranini, Arianna Salati, Valentina Sunda, and Chryssostomos Chatgilialoglu
- Subjects
sapienic acid ,palmitoleic acid ,membrane lipidomics ,red blood cell membrane ,fatty acid balance ,gas chromatographic resolution ,geometrical and positional isomers ,membrane fatty acid biomarker ,Medicine (General) ,R5-920 - Abstract
Fatty acids, as structural components of membranes and inflammation/anti-inflammatory mediators, have well-known protective and regulatory effects. They are studied as biomarkers of pathological conditions, as well as saturated and unsaturated hydrophobic moieties in membrane phospholipids that contribute to homeostasis and physiological functions. Lifestyle, nutrition, metabolism and stress—with an excess of radical and oxidative processes—cause fatty acid changes that are examined in the human body using blood lipids. Fatty acid-based membrane lipidomics represents a powerful diagnostic tool for assessing the quantity and quality of fatty acid constituents and also for the follow-up of the membrane fatty acid remodeling that is associated with different physiological and pathological conditions. This review focuses on fatty acid biomarkers with two examples of recent lipidomic research and health applications: (i) monounsaturated fatty acids and the analytical challenge offered by hexadecenoic fatty acids (C16:1); and (ii) the cohort of 10 fatty acids in phospholipids of red blood cell membranes and its connections to metabolic and nutritional status in healthy and diseased subjects.
- Published
- 2016
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38. Effects of elaidic acid on lipid metabolism in HepG2 cells, investigated by an integrated approach of lipidomics, transcriptomics and proteomics.
- Author
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Lone Vendel Nielsen, Toke P Krogager, Clifford Young, Carla Ferreri, Chryssostomos Chatgilialoglu, Ole Nørregaard Jensen, and Jan J Enghild
- Subjects
Medicine ,Science - Abstract
Trans fatty acid consumption in the human diet can cause adverse health effects, such as cardiovascular disease, which is associated with higher total cholesterol, a higher low density lipoprotein-cholesterol level and a decreased high density lipoprotein-cholesterol level. The aim of the study was to elucidate the hepatic response to the most abundant trans fatty acid in the human diet, elaidic acid, to help explain clinical findings on the relationship between trans fatty acids and cardiovascular disease. The human HepG2 cell line was used as a model to investigate the hepatic response to elaidic acid in a combined proteomic, transcriptomic and lipidomic approach. We found many of the proteins responsible for cholesterol synthesis up-regulated together with several proteins involved in the esterification and hepatic import/export of cholesterol. Furthermore, a profound remodeling of the cellular membrane occurred at the phospholipid level. Our findings contribute to the explanation on how trans fatty acids from the diet can cause modifications in plasma cholesterol levels by inducing abundance changes in several hepatic proteins and the hepatic membrane composition.
- Published
- 2013
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39. Biomimetic Models of Radical Stress and Related Biomarkers
- Author
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Chryssostomos Chatgilialoglu, Carla Ferreri, Annalisa Masi, Michele Melchiorre, Anna Sansone, Michael A. Terzidis, and Armida Torreggiani
- Subjects
Biomarkers ,Cyclonucleosides ,Free radicals ,Tandem protein-lipid damage ,Trans lipids ,Chemistry ,QD1-999 - Abstract
The biological consequences of free radical production is the central subject of a very lively scientific debate, focusing on the estimation of the type and extent of damage, as well as the efficiency of the protective and repair systems. When studying free radical based chemical mechanisms, it is very important to establish biomimetic models, which allow the experiments to be performed in a simplified environment, but suitably designed to be in strict connection with cellular conditions. The biomimetic modeling approach has been coupled with physical organic chemistry methodologies and knowledge of free radical reactivity. Molecular basis of important processes have been identified, building up molecular libraries of products concerning unsaturated lipids, sulfur-containing proteins and nucleic acids, to be developed as biomarkers. Ongoing projects in our group deal with lipidomics, genomics and proteomics of free radical stress and some examples will be described.
- Published
- 2012
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40. Biomimetic Chemistry on Tandem Protein/Lipid Damages under Reductive Radical Stress
- Author
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Sílvia Atrian, Krzysztof Bobrowski, Mercè Capdevila, Chryssostomos Chatgilialoglu, Carla Ferreri, Chantal Houée-Levin, Anna Maria Salzano, Andrea Scaloni, and Armida Torreggiani
- Subjects
Lipids ,Peptides ,Radicals ,Radiolysis ,Reductive stress ,Chemistry ,QD1-999 - Abstract
The study of radical stress in the biological environment needs a comprehensive vision of all possible reactive species and their mechanisms. Among them, reductive stress is evaluated for its selective target of sulfur-containing compounds. The selective attack of reducing species like H• atoms or eaq?/H+ to sulfur-containing amino acid residues has been proved in different substrates, peptides and proteins. The transformations include methionine to ?-aminobutyric acid and cysteine/cystine residues to alanine, as recognized in several sequences so far, such as RNase A, lysozyme, Met-enkephalin, amyloid ?-peptide and metallothioneins. The amino acid desulfurization is accompanied by the formation of low-molecular-weight sulfur-centered radicals that may cause geometrical cis–trans isomerization of unsaturated fatty acid residues in lipid bilayer. Thus, tandem protein/lipid damage is accomplished. Progress in research has given us a more comprehensive overview of the protein modifications and their roles, and the chemical biology approach will make its vital contribution to the study of free radical reactions, linking chemistry to biology and medicine.
- Published
- 2008
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41. Lipidomics and Free Radical Modifications of Lipids
- Author
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Chryssostomos Chatgilialoglu, Carla Ferreri, Albin Hermetter, Emmanuel Lacote, Branka Mihaljević, Athanassios Nicolaides, and Athanassia Siafaka-Kapadai
- Subjects
Lipid isomerization ,Lipid peroxidation ,Lipidomics ,Peroxy lipids ,Trans fatty acids ,Chemistry ,QD1-999 - Abstract
The free-radical-induced modification of biologically relevant molecules is an active field of interdisciplinary research, spanning from chemistry to biochemistry, biology and medicine. Lipid modifications are also attracting attention for their relationship with structural and functional roles in physiological and pathological conditions of living organisms. The discipline of lipidomics studies the lipid behavior in an innovative and multidisciplinary context. Combining lipidomics with free radical chemistry, the research field becomes an ideal setting for the chemical biology approach, to study the basis of molecular mechanisms and chemical reactivity and connect them with free-radical-based processes occurring in the biological environment. This paper will give an overview of the approaches for studying free radical processes on lipids and some biological consequences, which represent also subjects of interdisciplinary collaborations among European research groups and contribute to the general topic of the COST Action 'Free Radicals in Chemical Biology'.
- Published
- 2008
- Full Text
- View/download PDF
42. Free Radicals in Chemical Biology
- Author
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Chryssostomos Chatgilialoglu
- Subjects
Chemistry ,QD1-999 - Published
- 2008
- Full Text
- View/download PDF
43. DNA Damage and Radical Reactions: Mechanistic Aspects, Formation in Cells and Repair Studies
- Author
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Jean Cadet, Thomas Carell, Luciano Cellai, Chryssostomos Chatgilialoglu, Thanasis Gimisis, Miguel Miranda, Peter O'Neill, Jean-Luc Ravanat, and Marc Robert
- Subjects
Base excision repair ,Dna ,Guanine radical cation ,Pathway ,Chemistry ,QD1-999 - Abstract
Several examples of oxidative and reductive reactions of DNA components that lead to single and tandem modifications are discussed in this review. These include nucleophilic addition reactions of the one-electron oxidation-mediated guanine radical cation and the one-electron reduced intermediate of 8-bromopurine 2'-deoxyribonucleosides that give rise to either an oxidizing guanine radical or related 5',8-cyclopurine nucleosides. In addition, mechanistic insights into the reductive pathways involved in the photolyase induced reversal of cyclobutadipyrimidine and pyrimidine (6-4) pyrimidone photoproducts are provided. Evidence for the occurrence and validation in cellular DNA of •OH radical degradation pathways of guanine that have been established in model systems has been gained from the accurate measurement of degradation products. Relevant information on biochemical aspects of the repair of single and clustered oxidatively generated damage to DNA has been gained from detailed investigations that rely on the synthesis of suitable modified probes. Thus the preparation of stable carbocyclic derivatives of purine nucleoside containing defined sequence oligonucleotides has allowed detailed crystallographic studies of the recognition step of the base damage by enzymes implicated in the base excision repair (BER) pathway. Detailed insights are provided on the BER processing of non–double strand break bistranded clustered damage that may consist of base lesions, a single strand break or abasic sites and represent one of the main deleterious classes of radiation-induced DNA damage.
- Published
- 2008
- Full Text
- View/download PDF
44. Biologically Relevant Small Radicals
- Author
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Georg Bauer, Gabor Speier, Gabor Merenyi, Jozsef Kaizer, Sara Goldstein, Bernard T. Golding, Georg Gescheidt, Lidia Gebicka, Jerzy L. Gebicki, Chryssostomos Chatgilialoglu, and Peter Wardman
- Subjects
Antioxidants ,Reactive carbon species ,Reactive oxygen species ,Reactive nitrogen species ,Reactive sulfur species ,Signaling pathways ,Chemistry ,QD1-999 - Abstract
Biologically relevant small radicals are at the focus of the working group 4 (WG4) of the COST Action CM0603 (Free Radicals in Chemical Biology, CHEMBIORADICAL). This article surveys the areas of research being undertaken by the partners in WG4. The character of the radicals is described together with experimental techniques utilized to follow their structure and reactivity. Specifically, C-, S-, N- and O-centered radicals of small size, and their interaction with different biomolecules are described. Processes at the molecular level exemplifying important biological signaling and damaging pathways are introduced.
- Published
- 2008
- Full Text
- View/download PDF
45. A rare genetic disorder provides insights into mechanisms of early-onset neurodegeneration
- Author
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Cherif Badja, Sophie Momen, Gene Ching Cheik Koh, Soraya Boushaki, Theodoros I. Roumeliotis, Zuza Kozik, Ian Jones, Vicky Bousgouni, João M. L. Dias, Marios G. Krokidis, Jamie Young, Hongwei Chen, Ming Yang, France Docquier, Yasin Memari, Lorea Valcarcel-Jimenez, Komal Gupta, Li Ren Kong, Heather Fawcett, Florian Robert, Salome Zhao, Andrea Degasperi, Helen Davies, Rebecca Harris, Christian Frezza, Chryssostomos Chatgilialoglu, Robert Sarkany, Alan Lehmann, Chris Bakal, Jyoti Choudhary, Hiva Fassihi, and Serena Nik-Zainal
- Abstract
Xeroderma pigmentosum (XP) is characterized by defective repair of ultraviolet radiation(UVR)-induced DNA damage. Patients have UVR hypersensitivity and increased skin cancer risk. Effective photoprotection has reduced childhood cancer-related deaths, but revealed adolescence-onset neurodegeneration, arising through unknown mechanisms. Here, we investigate XP neurodegeneration using pluripotent stem cells derived from XP patients and healthy relatives, performing functional multi-omics on samples during neuronal differentiation. We find endoplasmic reticulum stress is upregulated, preceded by oxidative stress, causing substantial 5’,8-cyclopurine and 8-oxopurine DNA damage. Critically, XP neurons exhibit inappropriate downregulation of the protein clearance ubiquitin-proteasome system (UPS). Chemical enhancement of UPS activity improves phenotypes, albeit inadequately, implying that early detection/prevention strategies are necessary to produce clinically impactful outcomes. Thus, we develop an early detection assay predicting neurodegeneration in at-risk patients.
- Published
- 2023
- Full Text
- View/download PDF
46. Geometrical isomerization of arachidonic acid during lipid peroxidation interferes with ferroptosis
- Author
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Yusuke Hirata, Carla Ferreri, Yuto Yamada, Aya Inoue, Anna Sansone, Fabrizio Vetica, Wakana Suzuki, Saya Takano, Takuya Noguchi, Atsushi Matsuzawa, and Chryssostomos Chatgilialoglu
- Subjects
Physiology (medical) ,Biochemistry - Published
- 2023
- Full Text
- View/download PDF
47. Tris(trimethylsilyl)silane
- Author
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Bernd Giese, Joachim Dickhaut, Chryssostomos Chatgilialoglu, Xiaoyu Wu, and Zhaoguo Zhang
- Published
- 2022
- Full Text
- View/download PDF
48. Membrane Lipidomics for Personalized Health
- Author
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Carla Ferreri, Chryssostomos Chatgilialoglu
- Published
- 2015
49. Evaluation of Hydroxyl Radical Reactivity by Thioether Group Proximity in Model Peptide Backbone: Methionine versus S-Methyl-Cysteine
- Author
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Chryssostomos Chatgilialoglu, Magdalena Grzelak, Konrad Skotnicki, Piotr Filipiak, Franciszek Kazmierczak, Gordon L. Hug, Krzysztof Bobrowski, and Bronislaw Marciniak
- Subjects
Hydroxyl Radical ,Organic Chemistry ,General Medicine ,Sulfides ,Catalysis ,Computer Science Applications ,Inorganic Chemistry ,Methionine ,methionine ,S-methyl-cysteine ,pulse and γ-radiolysis ,oxidation ,free radicals ,high-resolution MS/MS ,Tandem Mass Spectrometry ,Cysteine ,Physical and Theoretical Chemistry ,Peptides ,Pulse Radiolysis ,Molecular Biology ,Oxidation-Reduction ,Spectroscopy - Abstract
Hydroxyl radicals (HO•) have long been regarded as a major source of cellular damage. The reaction of HO• with methionine residues (Met) in peptides and proteins is a complex multistep process. Although the reaction mechanism has been intensively studied, some essential parts remain unsolved. In the present study we examined the reaction of HO• generated by ionizing radiation in aqueous solutions under anoxic conditions with two compounds representing the simplest model peptide backbone CH3C(O)NHCHXC(O)NHCH3, where X = CH2CH2SCH3 or CH2SCH3, i.e., the Met derivative in comparison with the cysteine-methylated derivative. We performed the identification and quantification of transient species by pulse radiolysis and final products by LC–MS and high-resolution MS/MS after γ-radiolysis. The results allowed us to draw for each compound a mechanistic scheme. The fate of the initial one-electron oxidation at the sulfur atom depends on its distance from the peptide backbone and involves transient species of five-membered and/or six-membered ring formations with different heteroatoms present in the backbone as well as quite different rates of deprotonation in forming α-(alkylthio)alkyl radicals.
- Published
- 2022
50. Critical Review on Fatty Acid-Based Food and Nutraceuticals as Supporting Therapy in Cancer
- Author
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Carla Ferreri, Anna Sansone, Chryssostomos Chatgilialoglu, Rosaria Ferreri, Javier Amézaga, Mercedes Caro Burgos, Sara Arranz, and Itziar Tueros
- Subjects
Organic Chemistry ,Fatty Acids ,General Medicine ,Catalysis ,Computer Science Applications ,Inorganic Chemistry ,Membrane Lipids ,Neoplasms ,Dietary Supplements ,Fatty Acids, Unsaturated ,Humans ,Physical and Theoretical Chemistry ,Molecular Biology ,Spectroscopy - Abstract
Fatty acids have an important place in both biological and nutritional contexts and, from a clinical point of view, they have known consequences for diseases’ onset and development, including cancer. The use of fatty acid-based food and nutraceuticals to support cancer therapy is a multidisciplinary subject, involving molecular and clinical research. Knowledge regarding polyunsaturated fatty acids essentiality/oxidizability and the role of lipogenesis-desaturase pathways for cell growth, as well as oxidative reactivity in cancer cells, are discussed, since they can drive the choice of fatty acids using their multiple roles to support antitumoral drug activity. The central role of membrane fatty acid composition is highlighted for the application of membrane lipid therapy. As fatty acids are also known as biomarkers of cancer onset and progression, the personalization of the fatty acid-based therapy is also possible, taking into account other important factors such as formulation, bioavailability and the distribution of the supplementation. A holistic approach emerges combining nutra- and pharma-strategies in an appropriate manner, to develop further knowledge and applications in cancer therapy.
- Published
- 2022
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