Proteomic identification of HNE-bound proteins in early Alzheimer disease: Insights into the role of lipid peroxidation in the progression of AD

Reed, Tanea T.; Pierce, William M.; Markesbery, William R.; Butterfield, D. Allan

doi:10.1016/j.brainres.2009.04.009

Cited by 183 publications

(168 citation statements)

References 74 publications

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“…In late-stage AD, redox proteomics identified four HNEmodified proteins that overlap EAD (Eno1, ATP synthase, MnSOD, and CRMP2) (304,322). Both Eno1 and ATP synthase are consistently HNE modified in all transitional stages of AD, providing evidence for the altered energy metabolism and mitochondrial dysfunction hypotheses associated in the progression of AD (66,160,175).…”

Section: Ead Carbonylated Proteinsmentioning

confidence: 99%

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Redox Proteomics in Selected Neurodegenerative Disorders: From Its Infancy to Future Applications

Butterfield

Perluigi

Reed

et al. 2012

Antioxidants & Redox Signaling

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153

134

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Several studies demonstrated that oxidative damage is a characteristic feature of many neurodegenerative diseases. The accumulation of oxidatively modified proteins may disrupt cellular functions by affecting protein expression, protein turnover, cell signaling, and induction of apoptosis and necrosis, suggesting that protein oxidation could have both physiological and pathological significance. For nearly two decades, our laboratory focused particular attention on studying oxidative damage of proteins and how their chemical modifications induced by reactive oxygen species/reactive nitrogen species correlate with pathology, biochemical alterations, and clinical presentations of Alzheimer's disease. This comprehensive article outlines basic knowledge of oxidative modification of proteins and lipids, followed by the principles of redox proteomics analysis, which also involve recent advances of mass spectrometry technology, and its application to selected age-related neurodegenerative diseases. Redox proteomics results obtained in different diseases and animal models thereof may provide new insights into the main mechanisms involved in the pathogenesis and progression of oxidativestress-related neurodegenerative disorders. Redox proteomics can be considered a multifaceted approach that has the potential to provide insights into the molecular mechanisms of a disease, to find disease markers, as well as to identify potential targets for drug therapy. Considering the importance of a better understanding of the cause/effect of protein dysfunction in the pathogenesis and progression of neurodegenerative disorders, this article provides an overview of the intrinsic power of the redox proteomics approach together with the most significant results obtained by our laboratory and others during almost 10 years of research on neurodegenerative disorders since we initiated the field of redox proteomics. Antioxid. Redox Signal. 17, 1610-1655.

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Section: Ead Carbonylated Proteinsmentioning

confidence: 99%

“…These proteins include Eno1 and ATP synthase, which were just discussed. Additionally, triose phosphate isomerase, malate dehydogenase, MnSOD, and DRP2 (CRMP2) undergo HNE conjugation in EAD brain as identified by redox proteomics (322).…”

Section: Ead Carbonylated Proteinsmentioning

confidence: 99%

Redox Proteomics in Selected Neurodegenerative Disorders: From Its Infancy to Future Applications

Butterfield

Perluigi

Reed

et al. 2012

Antioxidants & Redox Signaling

Self Cite

153

134

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“…In order to identify the protein targets of reactive carbonyl compounds that have been detected by western blotting on one-or two-dimensional SDS-polyacrylamide gels, mass spectrometry analysis of the gel spot or band on an equivalent Coomassie-stained gel is often carried out [109,110], as mass spectrometry is the most informative and reliable technique for this purpose. The spots of interest are excised from the gel and digested to peptides, an enzymatic process usually carried out using trypsin, but other proteases such as AspN or GluC can be used [111].…”

Section: -[(Hept-1-enyl)-4-hexylpyridinium]lysine (Hhp-lysine) a Nomentioning

confidence: 99%

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

Sousa

Pitt

Spickett

2017

Free Radical Biology and Medicine

134

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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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“…[5][6][7][8][9] An important example is 4-hydroxynonenal, a highly reactive lipid peroxidation product that is increased in the brains of stroke victims and neurodegenerative disease, and is capable of forming protein adducts and stimulating the formation of other reactive species. [5][6][7][8][9][10][11][12][13] Physiologically, the concentration of free HNE in human blood ranges from 0.069 ± 0.015 μM for healthy subjects under the age of 30, and increases to 0.107 ± 0.027 μM for individuals over age 70. 14 Pathologically, levels increase substantially due to the initiation of lipid peroxidation with free levels reported in the range of 1-10 μM how cellular metabolic activities regulate autophagy and determine the susceptibility to oxidative stress and ultimately cell death in neuronal cells is not well understood.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of glycolysis attenuates 4-hydroxynonenal-dependent autophagy and exacerbates apoptosis in differentiated SH-SY5Y neuroblastoma cells

et al. 2013

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Proteomic identification of HNE-bound proteins in early Alzheimer disease: Insights into the role of lipid peroxidation in the progression of AD

Cited by 183 publications

References 74 publications

Redox Proteomics in Selected Neurodegenerative Disorders: From Its Infancy to Future Applications

Redox Proteomics in Selected Neurodegenerative Disorders: From Its Infancy to Future Applications

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

Inhibition of glycolysis attenuates 4-hydroxynonenal-dependent autophagy and exacerbates apoptosis in differentiated SH-SY5Y neuroblastoma cells

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