Protein lipoxidation: Detection strategies and challenges
Enzymatic and non-enzymatic lipid metabolism can give rise to reactive species that may covalently modify cellular or plasma proteins through a process known as lipoxidation. Under basal conditions, protein lipoxidation can contribute to normal cell homeostasis and participate in signaling or adapti...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2015-08-01
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| Series: | Redox Biology |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213231715000464 |
| _version_ | 1818572788175208448 |
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| author | Giancarlo Aldini M. Rosário Domingues Corinne M. Spickett Pedro Domingues Alessandra Altomare Francisco J. Sánchez-Gómez Clara L. Oeste Dolores Pérez-Sala |
| author_facet | Giancarlo Aldini M. Rosário Domingues Corinne M. Spickett Pedro Domingues Alessandra Altomare Francisco J. Sánchez-Gómez Clara L. Oeste Dolores Pérez-Sala |
| author_sort | Giancarlo Aldini |
| collection | DOAJ |
| description | Enzymatic and non-enzymatic lipid metabolism can give rise to reactive species that may covalently modify cellular or plasma proteins through a process known as lipoxidation. Under basal conditions, protein lipoxidation can contribute to normal cell homeostasis and participate in signaling or adaptive mechanisms, as exemplified by lipoxidation of Ras proteins or of the cytoskeletal protein vimentin, both of which behave as sensors of electrophilic species. Nevertheless, increased lipoxidation under pathological conditions may lead to deleterious effects on protein structure or aggregation. This can result in impaired degradation and accumulation of abnormally folded proteins contributing to pathophysiology, as may occur in neurodegenerative diseases. Identification of the protein targets of lipoxidation and its functional consequences under pathophysiological situations can unveil the modification patterns associated with the various outcomes, as well as preventive strategies or potential therapeutic targets. Given the wide structural variability of lipid moieties involved in lipoxidation, highly sensitive and specific methods for its detection are required. Derivatization of reactive carbonyl species is instrumental in the detection of adducts retaining carbonyl groups. In addition, use of tagged derivatives of electrophilic lipids enables enrichment of lipoxidized proteins or peptides. Ultimate confirmation of lipoxidation requires high resolution mass spectrometry approaches to unequivocally identify the adduct and the targeted residue. Moreover, rigorous validation of the targets identified and assessment of the functional consequences of these modifications are essential. Here we present an update on methods to approach the complex field of lipoxidation along with validation strategies and functional assays illustrated with well-studied lipoxidation targets. Keywords: Mass spectrometry, Reactive carbonyl species, Electrophilic lipids, Cyclopentenone prostaglandins, Target validation, Vimentin cysteine lipoxidation |
| first_indexed | 2024-12-15T00:02:20Z |
| format | Article |
| id | doaj.art-170a7c81bbe2474ab98bb10e6cb9258e |
| institution | Directory Open Access Journal |
| issn | 2213-2317 |
| language | English |
| last_indexed | 2024-12-15T00:02:20Z |
| publishDate | 2015-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Redox Biology |
| spelling | doaj.art-170a7c81bbe2474ab98bb10e6cb9258e2022-12-21T22:42:52ZengElsevierRedox Biology2213-23172015-08-015253266Protein lipoxidation: Detection strategies and challengesGiancarlo Aldini0M. Rosário Domingues1Corinne M. Spickett2Pedro Domingues3Alessandra Altomare4Francisco J. Sánchez-Gómez5Clara L. Oeste6Dolores Pérez-Sala7Department of Pharmaceutical Sciences, Università degli Studi di Milano, Via Mangiagalli 25, 20133 Milan, ItalyMass Spectrometry Centre, QOPNA, Department of Chemistry, University of Aveiro, Aveiro 3810-193, PortugalSchool of Life and Health Sciences, Aston Triangle, Aston University, Birmingham B4 7ET, UKMass Spectrometry Centre, QOPNA, Department of Chemistry, University of Aveiro, Aveiro 3810-193, PortugalDepartment of Pharmaceutical Sciences, Università degli Studi di Milano, Via Mangiagalli 25, 20133 Milan, ItalyDepartment of Chemical and Physical Biology, Centro de Investigaciones Biológicas, CSIC, Ramiro de Maeztu, 9, Madrid 28040, SpainDepartment of Chemical and Physical Biology, Centro de Investigaciones Biológicas, CSIC, Ramiro de Maeztu, 9, Madrid 28040, SpainDepartment of Chemical and Physical Biology, Centro de Investigaciones Biológicas, CSIC, Ramiro de Maeztu, 9, Madrid 28040, Spain; Corresponding author.Enzymatic and non-enzymatic lipid metabolism can give rise to reactive species that may covalently modify cellular or plasma proteins through a process known as lipoxidation. Under basal conditions, protein lipoxidation can contribute to normal cell homeostasis and participate in signaling or adaptive mechanisms, as exemplified by lipoxidation of Ras proteins or of the cytoskeletal protein vimentin, both of which behave as sensors of electrophilic species. Nevertheless, increased lipoxidation under pathological conditions may lead to deleterious effects on protein structure or aggregation. This can result in impaired degradation and accumulation of abnormally folded proteins contributing to pathophysiology, as may occur in neurodegenerative diseases. Identification of the protein targets of lipoxidation and its functional consequences under pathophysiological situations can unveil the modification patterns associated with the various outcomes, as well as preventive strategies or potential therapeutic targets. Given the wide structural variability of lipid moieties involved in lipoxidation, highly sensitive and specific methods for its detection are required. Derivatization of reactive carbonyl species is instrumental in the detection of adducts retaining carbonyl groups. In addition, use of tagged derivatives of electrophilic lipids enables enrichment of lipoxidized proteins or peptides. Ultimate confirmation of lipoxidation requires high resolution mass spectrometry approaches to unequivocally identify the adduct and the targeted residue. Moreover, rigorous validation of the targets identified and assessment of the functional consequences of these modifications are essential. Here we present an update on methods to approach the complex field of lipoxidation along with validation strategies and functional assays illustrated with well-studied lipoxidation targets. Keywords: Mass spectrometry, Reactive carbonyl species, Electrophilic lipids, Cyclopentenone prostaglandins, Target validation, Vimentin cysteine lipoxidationhttp://www.sciencedirect.com/science/article/pii/S2213231715000464 |
| spellingShingle | Giancarlo Aldini M. Rosário Domingues Corinne M. Spickett Pedro Domingues Alessandra Altomare Francisco J. Sánchez-Gómez Clara L. Oeste Dolores Pérez-Sala Protein lipoxidation: Detection strategies and challenges Redox Biology |
| title | Protein lipoxidation: Detection strategies and challenges |
| title_full | Protein lipoxidation: Detection strategies and challenges |
| title_fullStr | Protein lipoxidation: Detection strategies and challenges |
| title_full_unstemmed | Protein lipoxidation: Detection strategies and challenges |
| title_short | Protein lipoxidation: Detection strategies and challenges |
| title_sort | protein lipoxidation detection strategies and challenges |
| url | http://www.sciencedirect.com/science/article/pii/S2213231715000464 |
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