Sequestering Agents of Intermediate Reactive Aldehydes as Inhibitors of Advanced Lipoxidation End‐Products (ALEs)

Carini, Marina; Facino, Roberto Maffei

doi:10.1002/0471973122.ch27

Cited by 2 publications

(3 citation statements)

References 161 publications

(198 reference statements)

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“…4‐Hydroxy‐ trans ‐2‐nonenal (HNE) is the most abundant and toxic α,β‐unsaturated aldehyde generated through the β‐cleavage of hydroperoxides from ω‐6 PUFAs,1 which plays a key role in a variety of pathophysiological processes, including Alzheimer's and Parkinson's diseases, liver fibrosis, glomerusclerosis, chronic obstructive bronco‐pulmonary diseases and atherosclerosis (see reviews2–5).…”

Section: Introductionmentioning

confidence: 99%

Mass spectrometric characterization of covalent modification of human serum albumin by 4‐hydroxy‐trans‐2‐nonenal

et al. 2006

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Several pieces of evidence indicate that albumin modified by HNE is a promising biomarker of systemic oxidative stress and that HNE-modified albumin may contribute to the immune reactions triggered by lipid peroxidation-derived antigens. In this study, we found by HPLC analysis that HNE is rapidly quenched by human serum albumin (HSA) because of the covalent adduction to the different accessible nucleophilic residues of the protein, as demonstrated by electrospray ionization mass spectrometry (ESI-MS) direct infusion experiments (one to nine HNE adducts, depending on the molar ratio used, from 1:0.25 to 1:5 HSA:HNE). An LC-ESI-MS/MS approach was then applied to enzymatically digested HNE-modified albumin, which permitted the identification of 11 different HNE adducts, 8 Michael adducts (MA) and 3 Schiff bases (SB), involving nine nucleophilic sites, namely: His67 (MA), His146 (MA), His242 (MA), His288 (MA), His510 (MA), Lys 195 (SB), Lys 199 (MA, SB), Lys525 (MA, SB) and Cys34 (MA). The most reactive HNE-adduction site was found to be Cys34 (MA) followed by Lys199, which primarily reacts through the formation of a Schiff base, and His146, giving the corresponding HNE Michael adduct. These albumin modifications are suitable tags of HNE-adducted albumin and could be useful biomarkers of oxidative and carbonylation damage in humans.

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Section: Introductionmentioning

confidence: 99%

Mass spectrometric characterization of covalent modification of human serum albumin by 4‐hydroxy‐trans‐2‐nonenal

et al. 2006

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“…11,12 By considering RCS as both a cause or effective agents of human diseases, it is quite clear that an accurate and sensitive method to measure RCS in biological matrices is required to: (i) understand better the pathogenetic role of RCS; (ii) identify a biomarker of the onset and progression of the disease; and (iii) identify a tool for evaluating the efficacy of the RCS sequestering agents,a new class of compounds designed to prevent/ retard the carbonyl-related diseases is required. 13 How to measure reactive carbonyl species in biological matrices RCS analysis in biological matrices can be approached by measuring free aldehydes or the corresponding adducts with nucleophilic macromolecules or with the detoxifying peptides GSH 14 and carnosine. 15 Since the pioneering work of Esterbauer and Cheeseman (HNE measurement by HPLC analysis), 16 progress has been made, although the 'gold standard' is yet to be attained.…”

Section: Introductionmentioning

confidence: 99%

“…By contrast, RCS adducts with proteins, stable enough to undergo accumulation, represent suitable biomarkers of carbonyl formation. 1,13 Protein carbonylation is now mainly measured by immunological and spectroscopic techniques, following 2,4-dinitrophenylhydrazine derivatization. 23 Such techniques give a general index of protein carbonylation since they evaluate the total content of carbonylated proteins generated both by an adduction mechanism and by a direct oxidative reaction.…”

Section: Introductionmentioning

confidence: 99%

α,β-Unsaturated aldehydes adducts to actin and albumin as potential biomarkers of carbonylation damage

Aldini

Orioli

2007

Redox Report

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Reactive carbonyl species (RCS) generated by lipid peroxidation, leading to protein carbonylation, are involved in several human diseases. Protein carbonylation constitutes one of the best characterised biomarker of oxidative damage to proteins. Albumin and actin have been identified, through different proteomic approaches, as the main protein targets for RCS in plasma and tissues, respectively. By a combined LC-MS/MS and computational approach, we have demonstrated their high reactivity towards alpha,beta-unsaturated aldehydes, and established the stoichiometry of reaction with HNE and acrolein, as well as the amino acid residues more susceptible to carbonyl attack. A new mass spectrometric approach, based on LC-MS/MS analysis of tag HNE/ACR-modified peptides of carbonylated albumin and actin is proposed, and the advantages over the conventional methods for RCS and RCS-adducted protein analyses discussed.

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Sequestering Agents of Intermediate Reactive Aldehydes as Inhibitors of Advanced Lipoxidation End‐Products (ALEs)

Cited by 2 publications

References 161 publications

Mass spectrometric characterization of covalent modification of human serum albumin by 4‐hydroxy‐trans‐2‐nonenal

Mass spectrometric characterization of covalent modification of human serum albumin by 4‐hydroxy‐trans‐2‐nonenal

α,β-Unsaturated aldehydes adducts to actin and albumin as potential biomarkers of carbonylation damage

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