Puzzles, patterns… and LDL: a mass spectrometry view

Ana Reis

Research output: Contribution to journalArticle

Abstract

Oxidative modification to phospholipids by free radicals yields a myriad of structurally diverse compounds that can be classified as intermediate species (radical compounds), primary products (insertions of oxygen in the intact structure), and secondary products (fragmentation of the carbon chain at the site of modification). While the latter are regarded as end stage products of lipid peroxidation, they are often reactive carbonyl compounds (RCS) and can attack amino groups present in proteins and aminophospholipids leading to tertiary products (covalent cross-linked adducts). Despite the complexity of products from in vitro radical peroxidation of phospholipids with various chains lengths, as described above, data from studies in vivo reveal that physiologically the system progresses to a less varied set of products with a simpler and more predictable pattern.
In the past decade, studies of protein carbonylation by lipid peroxidation-derived RCS mostly focused on modification by 4-hydroxy-2-nonenal (HNE) have shown that carbonylated proteins undergo changes to their conformation, causing aggregation and ultimately cellular dysfunction. On the other hand, the role of RCS esterified to phosphocholines (PC) has been less studied, despite the fact that oxPC adducts of ApoB100 were previously described in atherosclerotic plaques by immuno-staining methods. Although very sensitive, these methods lack structural information on the adducts present. Mass spectrometry-based strategies that can help unravel these structural motifs are essential to understand the role of carbonylation in cardiovascular and age-related diseases. An even greater challenge will be to integrate the findings on carbonylated ApoB-100 protein with other Omics approaches to gain a comprehensive knowledge of biomolecules present in the LDL particles, and help solve the puzzle regarding the molecular motifs responsible for increased atherogenicity of oxLDL.
This research was supported by a Marie Curie Intra- European Fellowship within the 7th European Community Framework Program (IEF 255076).
Original languageEnglish
Article numberHermann Esterbauer Award Lecture
Pages (from-to)S238
Number of pages1
JournalFree Radical Biology and Medicine
Volume53
Issue numberSupplement 1
DOIs
Publication statusPublished - Sep 2012
EventSociety for Free Radical Research International 16th Biennial Meeting - Imperial College London, London, United Kingdom
Duration: 6 Sep 20129 Sep 2012

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    Integrated Omics for the global mapping of biomolecules in LDL

    Reis, A., Spickett, C. M. & Rudnitskaya, A., Sep 2012, In : Free Radical Biology and Medicine. 53, Supplement 1, p. S212 1 p., 0560.

    Research output: Contribution to journalConference abstract

  • Mapping oxidative modifications of PTEN

    Tveen Jensen, K., Calimport, S. R. G., Verrastro, I., Spickett, C. M. & Pitt, A. R., Sep 2012, In : Free Radical Biology and Medicine. 53, Supplement 1, p. S213 1 p., 0576.

    Research output: Contribution to journalConference abstract

  • Mass spectrometry analysis of modified bee venom phospholipase A2 in correlation with increased activity

    Pasha, S., Mahalka, A. K., Reis, A., Pitt, A. R., Kinnunen, P. K. J. & Spickett, C. M., 2 Sep 2012, In : Free Radical Biology and Medicine. 53, Supplement 1, p. S213-S214 2 p., 0578.

    Research output: Contribution to journalConference abstract

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