Protein lipoxidation: detection strategies and challenges

Giancarlo Aldini, M. Rosário Domingues, Corinne M. Spickett, Pedro Domingues, Alessandra Altomare, Francisco J. Sánchez-Gómez, Clara L. Oeste, Dolores Pérez-Sala

Research output: Contribution to journalArticle

Abstract

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.

LanguageEnglish
Pages253-266
Number of pages14
JournalRedox biology
Volume5
Early online date21 May 2015
DOIs
Publication statusPublished - Aug 2015

Fingerprint

Proteins
Neurodegenerative diseases
Lipids
ras Proteins
Cytoskeletal Proteins
Vimentin
Lipid Metabolism
Neurodegenerative Diseases
Mass spectrometry
Blood Proteins
Assays
Mass Spectrometry
Homeostasis
Agglomeration
Derivatives
Degradation
Peptides
Sensors
Therapeutics

Bibliographical note

© 2015 Published by Elsevier B.V.

Funding: MINECO SAF2012-36519 and ISCIII RETIC RD12/0013/0008 (Spain) to DPS; PEst-C/QUI/UI0062/2013, FCOMP-01-0124-FEDER-037296 to QOPNA research unit and RNEM-REDE/1504/REM/2005 to Portuguese National Mass Spectrometry Network by Fundação para a Ciência e a Tecnologia (FCT, Portugal), European Union, QREN, FEDER, and COMPETE to MRMD and PD. CMS acknowledges funding from the Engineering and Physical Sciences Research
Council, UK, EP/I017887/1 Cross-Disciplinary Research Landscape Award (the Proxomics Project). Collaboration among the authors’ laboratories has been supported by EU COST Action CM1001 on “Chemistry of non-enzymatic protein modification - modulation of protein structure and function”

Keywords

  • cyclopentenone prostaglandins
  • electrophilic lipids
  • mass spectrometry
  • reactive carbonyl species
  • target validation
  • vimentin cysteine lipoxidation

Cite this

Aldini, G., Domingues, M. R., Spickett, C. M., Domingues, P., Altomare, A., Sánchez-Gómez, F. J., ... Pérez-Sala, D. (2015). Protein lipoxidation: detection strategies and challenges. Redox biology, 5, 253-266. https://doi.org/10.1016/j.redox.2015.05.003
Aldini, Giancarlo ; Domingues, M. Rosário ; Spickett, Corinne M. ; Domingues, Pedro ; Altomare, Alessandra ; Sánchez-Gómez, Francisco J. ; Oeste, Clara L. ; Pérez-Sala, Dolores. / Protein lipoxidation : detection strategies and challenges. In: Redox biology. 2015 ; Vol. 5. pp. 253-266.
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Aldini, G, Domingues, MR, Spickett, CM, Domingues, P, Altomare, A, Sánchez-Gómez, FJ, Oeste, CL & Pérez-Sala, D 2015, 'Protein lipoxidation: detection strategies and challenges' Redox biology, vol. 5, pp. 253-266. https://doi.org/10.1016/j.redox.2015.05.003

Protein lipoxidation : detection strategies and challenges. / Aldini, Giancarlo; Domingues, M. Rosário; Spickett, Corinne M.; Domingues, Pedro; Altomare, Alessandra; Sánchez-Gómez, Francisco J.; Oeste, Clara L.; Pérez-Sala, Dolores.

In: Redox biology, Vol. 5, 08.2015, p. 253-266.

Research output: Contribution to journalArticle

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AU - Aldini, Giancarlo

AU - Domingues, M. Rosário

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AU - Domingues, Pedro

AU - Altomare, Alessandra

AU - Sánchez-Gómez, Francisco J.

AU - Oeste, Clara L.

AU - Pérez-Sala, Dolores

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N2 - 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.

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Aldini G, Domingues MR, Spickett CM, Domingues P, Altomare A, Sánchez-Gómez FJ et al. Protein lipoxidation: detection strategies and challenges. Redox biology. 2015 Aug;5:253-266. https://doi.org/10.1016/j.redox.2015.05.003