Site-specific proteomic analysis of lipoxidation adducts in cardiac mitochondria reveals chemical diversity of 2-alkenal adduction

Chavez, Juan D.; Wu, Jianyong; Bisson, William H.; Maier, Christoph

doi:10.1016/j.jprot.2011.03.031

Cited by 57 publications

(82 citation statements)

References 56 publications

(64 reference statements)

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“…However, this approach requires a prior knowledge of the modification specific mass increments. Thus, many proteomics experiments, aiming for the identification of oxoLPP-protein adducts, rely only on a few well-known oxoLPP species, such as HNE, hydroxy-hexenal (HHE), glyoxal, methylglyoxal and acrolein, assuming their presence in the sample [44], [87], [88], [89]. Alternatively, a number of database [90] or spectral library [91], [92], [93] search strategies for the identification of peptides with unconsidered PTMs are available, but require higher computational powers.…”

Section: Resultsmentioning

confidence: 99%

Cross-talk between lipid and protein carbonylation in a dynamic cardiomyocyte model of mild nitroxidative stress

et al. 2017

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Reactive oxygen and nitrogen species (ROS/RNS) play an important role in the regulation of cardiac function. Increase in ROS/RNS concentration results in lipid and protein oxidation and is often associated with onset and/or progression of many cardiovascular disorders. However, interplay between lipid and protein modifications has not been simultaneously studied in detail so far. Biomolecule carbonylation is one of the most common biomarkers of oxidative stress. Using a dynamic model of nitroxidative stress we demonstrated rapid changes in biomolecule carbonylation in rat cardiomyocytes. Levels of carbonylated species increased as early as 15 min upon treatment with the peroxynitrite donor, 3-morpholinosydnonimine (SIN-1), and decreased to values close to control after 16 h. Total (lipids+proteins) vs. protein-specific carbonylation showed different dynamics, with a significant increase in protein-bound carbonyls at later time points. Treatment with SIN-1 in combination with inhibitors of proteasomal and autophagy/lysosomal degradation pathways allowed confirmation of a significant role of the proteasome in the degradation of carbonylated proteins, whereas lipid carbonylation increased in the presence of autophagy/lysosomal inhibitors. Electrophilic aldehydes and ketones formed by lipid peroxidation were identified and relatively quantified using LC-MS/MS. Molecular identity of reactive species was used for data-driven analysis of their protein targets. Combination of different enrichment strategies with LC-MS/MS analysis allowed identification of more than 167 unique proteins with 332 sites modified by electrophilic lipid peroxidation products. Gene ontology analysis of modified proteins demonstrated enrichment of several functional categories including proteins involved in cytoskeleton, extracellular matrix, ion channels and their regulation. Using calcium mobilization assays, the effect of nitroxidative stress on the activity of several ion channels was further confirmed.

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Section: Resultsmentioning

confidence: 99%

Cross-talk between lipid and protein carbonylation in a dynamic cardiomyocyte model of mild nitroxidative stress

et al. 2017

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“…As such, identification of specific modified proteins and a better understanding of how the modification affects protein function is a necessary step. To date, several large proteomics studies have aided our understanding of both the specificity and localization of protein carbonyls in tissue, such as adipose, liver, skeletal muscle, plasma, lung, and cardiac tissue (46,48,49,(57)(58)(59)(60)(61). Mass-spectrometry-based approaches have allowed for the identification of hundreds of direct targets of 4-HNE, 4-HHE, and acrolein carbonylation targets with cytosolic, mitochondrial, ER, and nuclear localization.…”

Section: Lipid Peroxidation and Apoptosismentioning

confidence: 99%

Oxidative stress and lipotoxicity

Hauck

Bernlohr

2016

Journal of Lipid Research

234

175

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“…This affinity approach was subsequently applied to lipoxidation adducts in cardiac mitochondria, where adduction by acrolein, β-hydroxyacrolein, crotonaldehyde, 4-hydroxy-2-hexenal, 4-hydroxy-2-nonenal and 4-oxo-2-nonenal was observed [122]. A more recent study used ARP to quantify the susceptibility of proteins from hepatic mitochondria to HNE damage, using magnetic streptavidin beads for enrichment either at the level of modified protein or modified peptide after tryptic digestion [123].…”

Section: Zhu Et Al Incubated Chymotrypsin Cytochrome C β-Lactoglobmentioning

confidence: 99%

Chemistry and analysis of HNE and other prominent carbonyl-containing lipid oxidation compounds

Sousa

Pitt

Spickett

2017

Free Radical Biology and Medicine

141

105

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The process of lipid oxidation generates a diverse array of small aldehydes and carbonyl-containing compounds, which may occur in free form or esterified within phospholipids and cholesterol esters. These aldehydes mostly result from fragmentation of fatty acyl chains following radical oxidation, and the products can be subdivided into alkanals, alkenals (usually D,β-unsaturated), γ-substituted alkenals and bis-aldehydes.Isolevuglandins are non-fragmented di-carbonyl compounds derived from H 2 -isoprostanes, and oxidation of the ω-3-fatty acid docosahexenoic acid yield analogous 22 carbon neuroketals. Non-radical oxidation by hypochlorous acid can generate D-chlorofatty aldehydes from plasmenyl phospholipids. Most of these compounds are reactive and have generally been considered as toxic products of a deleterious process. The reactivity is especially high for the D,β-unsaturated alkenals, such as acrolein and crotonaldehyde, and for γ-substituted alkenals, of which 4-hydroxy-2-nonenal and 4-oxo-2-nonenal are best Page | 2 known. Nevertheless, in recent years several previously neglected aldehydes have been investigated and also found to have significant reactivity and biological effects; notable examples are 4-hydroxy-2-hexenal and 4-hydroxy-dodecadienal. This has led to substantial interest in the biological effects of all of these lipid oxidation products and their roles in disease, including proposals that HNE is a second messenger or signalling molecule.However, it is becoming clear that many of the effects elicited by these compounds relate to their propensity for forming adducts with nucleophilic groups on proteins, DNA and specific phospholipids. This emphasizes the need for good analytical methods, not just for free lipid oxidation products but also for the resulting adducts with biomolecules. The most informative methods are those utilizing HPLC separations and mass spectrometry, although analysis of the wide variety of possible adducts is very challenging. Nevertheless, evidence for the occurrence of lipid-derived aldehyde adducts in biological and clinical samples is building, and offers an exciting area of future research. AbbreviationsAcr-dG, 1,N2-propanodeoxyguanosine; AGEs, advanced glycation end-product; ALEs, advanced lipoxidation end product; ApoB100, apolipoprotein B100; ApoE, apolipoprotein E; ARP, aldehyde reactive probe; AspN, endoproteinase AspN (flavastacin); βLG, β-lactoglobulin; BHZ, biotin hydrazide; BN-PAGE, blue native polyacrylamide gel

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Site-specific proteomic analysis of lipoxidation adducts in cardiac mitochondria reveals chemical diversity of 2-alkenal adduction

Cited by 57 publications

References 56 publications

Cross-talk between lipid and protein carbonylation in a dynamic cardiomyocyte model of mild nitroxidative stress

Cross-talk between lipid and protein carbonylation in a dynamic cardiomyocyte model of mild nitroxidative stress

Oxidative stress and lipotoxicity

Chemistry and analysis of HNE and other prominent carbonyl-containing lipid oxidation compounds

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