Proteomic analysis of 4-hydroxy-2-nonenal-modified proteins in G93A-SOD1 transgenic mice-A model of familial amyotrophic lateral sclerosis

Perluigi, Marzia; Poon, H. Fai; Hensley, Kenneth; Pierce, William M.; Klein, Jon B.; Calabrese, Vittorio; Marco, C. De; Butterfield, D. Allan

doi:10.1016/j.freeradbiomed.2004.12.021

Cited by 144 publications

(94 citation statements)

References 52 publications

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“…In human brain, enolase exists in three molecular forms: non-neuronal enolase (␣, ␣Ј-enolase), neuron-specific enolase (NSE; ␥, ␥Ј-enolase, also known as 14-3-2 protein and neuron specific protein), and the short lived heterodimer ␣, ␥Ј-enolase. This enzyme has been studied extensively in AD brain, and recently our proteomic investigation has identified ␣-enolase as specifically oxidized in AD brain (39) and in the G93A-SOD1 transgenic mice model of fALS (40). Here we found not only an increase of ␣-enolase protein levels but also a parallel increment of its specific carbonyl levels.…”

Section: Discussionsupporting

confidence: 61%

Proteomic Analysis of Protein Expression and Oxidative Modification in R6/2 Transgenic Mice

Perluigi

Poon

Maragos

et al. 2005

Molecular & Cellular Proteomics

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Huntington disease (HD) is a hereditary neurodegenerative disorder characterized by motor, psychiatric, and cognitive symptoms. The genetic defect responsible for the onset of the disease, expansion of CAG repeats in exon 1 of the gene that codes for huntingtin on chromosome 4, has been unambiguously identified. On the other hand, the mechanisms by which the mutation causes the disease are not completely understood yet. However, defects in energy metabolism of affected cells may cause oxidative damage, which has been proposed as one of the underlying molecular mechanisms that participate in the etiology of the disease. In our effort to investigate the extent of oxidative damage occurring at the protein level, we used a parallel proteomic approach to identify proteins potentially involved in processes upstream or downstream of the disease-causing huntingtin in a well established HD mouse model (R6/2 transgenic mice). We have demonstrated that the expression levels of dihydrolipoamide S-succinyltransferase and aspartate aminotransferase increase consistently over the course of disease (10-week-old mice). In contrast, pyruvate dehydrogenase expression levels were found to be decreased in 10-week-old HD transgenic mice compared with young (4-week-old) mice. Our experimental approach also led to the identification of oxidatively modified proteins. Six proteins were found to be significantly oxidized in old R6/2 transgenic mice compared with either young transgenic mice or non-transgenic mice. These proteins are ␣-enolase, ␥-enolase (neuron-specific enolase), aconitase, the voltage-dependent anion channel 1, heat shock protein 90, and creatine kinase. Because oxidative damage has proved to play an important role in the pathogenesis and the progression of Huntington disease, our results for the first time identify specific oxidatively modified proteins that potentially contribute to the pathogenesis of Huntington disease.

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Section: Discussionsupporting

confidence: 61%

Proteomic Analysis of Protein Expression and Oxidative Modification in R6/2 Transgenic Mice

Perluigi

Poon

Maragos

et al. 2005

Molecular & Cellular Proteomics

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168

147

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“…We have also shown that α-enolase is oxidatively modified in AD and in various models of neurodegenerative disorders [32,82,83,90], indicating that this key protein is involved in several age-related neurodegenerative disorders. In addition, we have also shown that following caloric restriction in aging rats [93] and after treatment with lipoic acid in the SAMP8 mice [89], the specific carbonyl levels of α-enolase are significantly decreased leading us to believe that this protein may play a key role in the restoration of cognitive function.…”

Section: Energy Metabolismmentioning

confidence: 99%

“…When mutated, SOD can also cause disease as in the case of the neurodegenerative disorder, familial amyotrophic lateral sclerosis (fALS) [97]. The toxic gain of function of mutant SOD (mSOD) leads to the generation of reactive oxygen/ nitrogen species [83,91,114]. Some researchers believe that the elevated oxidative activity associated with mSOD occurs by enzymes acting as peroxidases [114] or as superoxide reductases [70] or by producing O 2 ·− to form peroxynitrite [94].…”

Section: Antioxidant and Cellular Detoxificationmentioning

confidence: 99%

Proteomic identification of brain proteins in the canine model of human aging following a long-term treatment with antioxidants and a program of behavioral enrichment: Relevance to Alzheimer's disease

Opii

Joshi

Head

et al. 2008

Neurobiology of Aging

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Aging and age-related disorders such as Alzheimer's disease (AD) are usually accompanied by oxidative stress as one of the main mechanisms contributing to neurodegeneration and cognitive decline. Aging canines develop cognitive dysfunction and neuropathology similar to those seen in humans, and the use of antioxidants results in reductions in oxidative damage and in improvement in cognitive function in this canine model of human aging. In the present study, the effect of a longterm treatment with an antioxidant fortified diet and a program of behavioral enrichment on oxidative damage was studied in aged canines. To identify the neurobiological mechanisms underlying these treatment effects, the parietal cortex from 23 beagle dogs (8.1-12.4 years) were treated for 2.8 years in one of four treatment groups: i.e., control food-control behavioral enrichment (CC); control food -behavioral enrichment (CE); antioxidant food-control behavioral enrichment (CA); and enriched environment -antioxidant fortified food (EA). We analyzed the levels of the oxidative stress biomarkers, i.e., protein carbonyls, 3-nitrotyroine (3NT), and the lipid peroxidation product, 4- Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author ManuscriptNeurobiol Aging. Author manuscript; available in PMC 2009 January 1. Published in final edited form as:Neurobiol Aging. 2008 January ; 29(1): 51-70. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript hydroxynonenal (HNE), and observed a decrease in their levels on all treatments when compared to control, with the most significant effects found in the combined treatment, EA. Since EA treatment was most effective, we also carried out a comparative proteomics study to identify specific brain proteins that were differentially expressed and used a parallel redox proteomics approach to identify specific brain proteins that were less oxidized following EA. The specific protein carbonyl levels of glutamate dehydrogenase [NAD (P)], glyceraldehyde-3-phosphate dehydrogenase (GAPDH), α-enolase, neurofilament triplet L protein, glutathione S-transferase (GST) and fascin actin bundling protein were significantly reduced in brain of EA-treated dogs compared to control. We also observed significant increases in expression of Cu/Zn superoxide dismutase, fructose-bisphosphate aldolase C, creatine kinase, glutamate dehydrogenase and glyceraldehyde-3-phosphate dehydrogenase. The increased expression of these proteins and in particular Cu/Zn SOD correlated with improved cognitive function. In addition, there was a significant increas...

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“…Hence, it is recommended that identification of oxidatively modified proteins by redox proteomics should be followed by functional assessment of the identified proteins. These functional studies may identify metabolic or structural consequences caused by oxidative modification (302,376). A number of previous studies showed that oxidation of proteins could lead to alterations in protein expression and gene regulation, protein turnover, modulation of cell signaling, induction of apoptosis, necrosis, etc., eventually leading to loss of cells and function (72).…”

Section: F Some Known Consequences Of Protein Oxidationmentioning

confidence: 99%

“…Redox proteomics studies in ALS transgenic mice. Studies from our laboratory and others applied redox proteomics approaches to identify selective protein modifications in the spinal cord of G93A-SOD1 transgenic mice in comparison with wild-type mice (302). Perluigi et al (302) identified proteins that were significantly modified by HNE in the spinal cord tissue of a model of fALS, G93A-SOD1 transgenic mice, including DRP-2 (CRMP2), Hsp70, and, possibly, Eno1.…”

Section: G93amentioning

confidence: 99%

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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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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Proteomic analysis of 4-hydroxy-2-nonenal-modified proteins in G93A-SOD1 transgenic mice-A model of familial amyotrophic lateral sclerosis

Cited by 144 publications

References 52 publications

Proteomic Analysis of Protein Expression and Oxidative Modification in R6/2 Transgenic Mice

Proteomic Analysis of Protein Expression and Oxidative Modification in R6/2 Transgenic Mice

Proteomic identification of brain proteins in the canine model of human aging following a long-term treatment with antioxidants and a program of behavioral enrichment: Relevance to Alzheimer's disease

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

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