Redox proteomic profiling of neuroketal-adducted proteins in human brain: Regional vulnerability at middle age increases in the elderly

Domínguez, Mayelín; Oliveira, Eliandre de; Odena, María Antonia; Portero, Manuel Aguilar; Pamplona, Reinald; Ferrer, Isidro

doi:10.1016/j.freeradbiomed.2016.02.034

Cited by 29 publications

(28 citation statements)

References 66 publications

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“…Hyperphosphorylated tau deposition in LC neurons is accompanied by increased neuroketal adducts, indicating oxidative stress damage , and reduced SOD1 immunoreactivity, suggesting reduced oxidative stress responses in the same neurons and arguing in favour of increased oxidative damage in the LC at early stage NFT pathology . Haemoglobin α and haemoglobin β/γ immunoreactivity is also reduced in LC neurons with hyperphosphorylated tau deposition, as previously reported in neurons of the cerebral cortex in AD .…”

Section: Discussionsupporting

confidence: 80%

Locus coeruleus at asymptomatic early and middle Braak stages of neurofibrillary tangle pathology

Andrés‐Benito

Fernández-Dueñas

Carmona

et al. 2017

Neuropathology Appl Neurobio

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Complex alteration of several metabolic pathways occurs in the LC accompanying NFT formation at early and middle asymptomatic stages of NFT pathology. Dopaminergic/noradrenergic denervation and increased expression of α adrenergic receptor in the hippocampus and amygdala occur at first stage of NFT pathology, suggesting compensatory activation in the face of decreased adrenergic input occurring before clinical evidence of cognitive impairment and depression.

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Section: Discussionsupporting

confidence: 80%

Locus coeruleus at asymptomatic early and middle Braak stages of neurofibrillary tangle pathology

Andrés‐Benito

Fernández-Dueñas

Carmona

et al. 2017

Neuropathology Appl Neurobio

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“…The fact that specific regions of the CNS exhibit differential vulnerabilities to aging and various neurodegenerative (NDD) and neuropsychiatric diseases (NPD) also reinforces the idea of the heterogeneity in neuronal responses to cell-damaging processes, in addition to specificity in the etiology of each pathology (Mattson and Magnus, 2006; Domínguez et al, 2016). So, in order to better understand the mechanisms which are involved in neuronal resistance/sensitivity to stress and death, it is crucial to define the cell vulnerability of the different brain regions in physiological conditions.…”

Section: Introductionmentioning

confidence: 78%

Specific Metabolomics Adaptations Define a Differential Regional Vulnerability in the Adult Human Cerebral Cortex

Cabré

Jové

Naudí

et al. 2016

Front. Mol. Neurosci.

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Brain neurons offer diverse responses to stresses and detrimental factors during development and aging, and as a result of both neurodegenerative and neuropsychiatric disorders. This multiplicity of responses can be ascribed to the great diversity among neuronal populations. Here we have determined the metabolomic profile of three healthy adult human brain regions—entorhinal cortex, hippocampus, and frontal cortex—using mass spectrometry-based technologies. Our results show the existence of a lessened energy demand, mitochondrial stress, and lower one-carbon metabolism (particularly restricted to the methionine cycle) specifically in frontal cortex. These findings, along with the better antioxidant capacity and lower mTOR signaling also seen in frontal cortex, suggest that this brain region is especially resistant to stress compared to the entorhinal cortex and hippocampus, which are more vulnerable regions. Globally, our results show the presence of specific metabolomics adaptations in three mature, healthy human brain regions, confirming the existence of cross-regional differences in cell vulnerability in the human cerebral cortex.

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“…at slightly different pIs and molecular weights, but with the same provided support for the existence of post-translational modifications [115]. Generally, the same approach has been used when investigating other types of lipoxidation, such as the occurrence of neuroketal adducts in brain of middle-aged and old individuals [76].…”

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

confidence: 97%

“…Moreover, isoLG adducts of PE were increased in hyperlipidemic and inflammatory conditions, such familial hypercholesterolemia in humans and high-fat diet induced obesity and hepatosteatosis in mice [75]. Analogous compounds called neuroketals can be formed from DHA via H 4 -neuroprostanes; these have been detected in brain tissue and age-related increases in protein adducts observed [76]. The emerging evidence on the role of isolevuglandins has been reviewed recently by Salomon [68].…”

Section: Isolevuglandinsmentioning

confidence: 99%

“…Salomon's group raised polyclonal antibodies against 15-E2-IsoK or 12-E2-IsoK adducts with keyhole limpet hemocyanin, and used them in an ELISA to measure the levels of these isolevuglandin adducts in the plasma from patients with atherosclerosis and with endstage renal disease [105]. A goat anti-neuroketal antibody is now commercially available and has been used to show increased levels of neuroketal adducts in elderly brain [76]. Recently, a monoclonal (mAb 27Q4) has been raised against nonenal-modified keyhole limpet hemocyanin, and used to investigate the presence of protein-bound 2-nonenal in vivo; it was found that the antibody recognises cis-and trans-N ε -…”

Section: Analysis Of Free Aldehydic Oxidation Products and Their Metamentioning

confidence: 99%

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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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Redox proteomic profiling of neuroketal-adducted proteins in human brain: Regional vulnerability at middle age increases in the elderly

Cited by 29 publications

References 66 publications

Locus coeruleus at asymptomatic early and middle Braak stages of neurofibrillary tangle pathology

Locus coeruleus at asymptomatic early and middle Braak stages of neurofibrillary tangle pathology

Specific Metabolomics Adaptations Define a Differential Regional Vulnerability in the Adult Human Cerebral Cortex

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

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