Protein modification and phospholipid oxidation

Spickett, C.M., Tveen-jensen, K., Reis, A. and Pitt, A.R. (2013). Protein modification and phospholipid oxidation. Free Radical Biology and Medicine, 65 (Suppl.), S15.

Abstract

Phospholipid oxidation can generate reactive and electrophilic products that are capable of modifying proteins, especially at cysteine, lysine and histidine residues. Such lipoxidation reactions are known to alter protein structure and function, both with gain of function and loss of activity effects. As well as potential importance in the redox regulation of cell behaviour, lipoxidation products in plasma could also be useful biomarkers for stress conditions. Although studies with antibodies suggested the occurrence of lipoxidation adducts on ApoB-100, these products had not previously been characterized at a molecular level. We have developed new mass spectrometry-based approaches to detect and locate adducts of oxidized phospholipids in plasma proteins, as well as direct oxidation modifications of proteins, which avoid some of the problems typically encountered with database search engines leading to erroneous identifications of oxidative PTMs. This approach uses accurate mass extracted ion chromatograms (XICs) of fragment ions from peptides containing oxPTMs, and allows multiple modifications to be examined regardless of the protein that contains them. For example, a reporter ion at 184.074 Da/e corresponding to phosphocholine indicated the presence of oxidized phosphatidylcholine adducts, while 2 reporter ions at 100.078 and 82.025 Da/e were selective for allysine. ApoB-100-oxidized phospholipid adducts were detected even in healthy human samples, as well as LDL from patients with inflammatory disease. Lipidomic studies showed that more than 350 different species of lipid were present in LDL, and were altered in disease conditions. LDL clearly represents a very complex carrier system and one that offers a rich source of information about systemic conditions, with potential as indicators of oxidative damage in ageing or inflammatory diseases.

Publication DOI: https://doi.org/10.1016/j.freeradbiomed.2013.08.140
Divisions: Life & Health Sciences > Biosciences
Life & Health Sciences
Life & Health Sciences > Pharmacy
Additional Information: SFRR - Europe 2013 Meeting "The new era of -omics in Free Radicals in Biology and Medicine", 23 - 25 Sep 2013, Athens, Greece.
Published Date: 2013-09-20
Authors: Spickett, C.M. ( 0000-0003-4054-9279)
Tveen-jensen, K.
Reis, A.
Pitt, A.R. ( 0000-0003-3619-6503)

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