Protein oxidation in the brain in Alzheimer's disease

Aksenov, Michael Y.; Aksenova, Marina; Butterfield, D. Allan; Geddes, James W.; Markesbery, William R.

doi:10.1016/s0306-4522(00)00580-7

Cited by 465 publications

(319 citation statements)

References 52 publications

Supporting

Mentioning

295

Contrasting

Unclassified

Order By: Relevance

“…This result is in agreement with previous studies from our group that have demonstrated that although both β-and γ-actin are oxidized in synaptosomes treated with Aβ(1-42), only β-actin is significantly modified in AD brain (Aksenov et al, 2001,Boyd-Kimball et al, 2005. Therefore, since Aβ peptide induces acrolein production in neurons (Mark et al, 1997,Butterfield et al, 2002, and this aldehyde is increased in AD brain (Lovell et al, 2001), is also possible that Aβ peptide-induced β-actin oxidation is mediated by acrolein.…”

Section: Discussionsupporting

confidence: 93%

“…Membranes were blocked in the presence of 3% bovine serum albumin (BSA) in TBS-T (10 mM Tris-HCl, pH 7.5, 150 mM NaCl, 0.05% Tween 20) for 1 h, followed by incubation with rabbit polyclonal antibody anti-DNP (1:100, Chemicon) for 1 h. The membrane were washed three times with TBS-T and incubated with alkaline-phosphatase (AP)-conjugated secondary antibody for 1 h (1:4000, Sigma). The specificity of primary antibodies has been previously demonstrated by experiments performed in our laboratory (Aksenov et al, 2001). Samples were developed using SigmaFast Tablets (BCIP/NBT) substrate, and blots were scanned into Adobe Photoshop (Adobe System, Inc., Mountain View, CA, USA) and quantified with Scion Image (PC version of Macintosh compatible NIH Image).…”

Section: Slot Blots: Protein Carbonyl Measurementmentioning

confidence: 85%

See 1 more Smart Citation

Acrolein induces selective protein carbonylation in synaptosomes

et al. 2007

Self Cite

View full text Add to dashboard Cite

Acrolein, the most reactive of the α,β-unsaturated aldehydes, is endogenously produced by lipid peroxidation, and has been found increased in the brain of patients with Alzheimer's disease. Although it is known that acrolein increases total protein carbonylation and impairs the function of selected proteins, no study has addressed which proteins are selectively carbonylated by this aldehyde. In this study we investigated the effect of increasing concentrations of acrolein (0, 0.005, 0.05, 0.5, 5, 50 μM) on protein carbonylation in gerbil synaptosomes. In addition, we applied proteomics to identify synaptosomal proteins that were selectively carbonylated by 0.5 μM acrolein. Acrolein increased total protein carbonylation in a dose-dependent manner. Proteomic analysis (2-D electrophoresis followed by mass spectrometry) revealed that tropomyosin-3-gamma isoform 2, tropomyosin-5, β-actin, mitochondrial Tu translation elongation factor (EFTu mt ) and voltagedependent anion channel (VDAC) were significantly carbonylated by acrolein. Consistent with the proteomics studies that have identified specifically oxidized proteins in Alzheimer's Disease (AD) brain, the proteins identified in this study are involved in a wide variety of cellular functions including energy metabolism, neurotransmission, protein synthesis, and cytoskeletal integrity. Our results suggest that acrolein may significantly contribute for oxidative damage in AD brain.Acrolein (2-propen-1-al), the most reactive of the α,β-unsaturated aldehydes (Esterbauer et al., 1991), is a toxic compound found in automobile exhaust gases, overheated cooking oils and a metabolite of cyclophosphamide and allyl alcohol (Halliwell and Gutteridge, 1999). Acrolein can also be endogenously produced as a product of lipid peroxidation (Adams and Klaidman, 1993,Uchida, 1999) and from polyamine metabolism (Takano et al., 2005 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 ManuscriptNeuroscience. Author manuscript; available in PMC 2008 July 13. Published in final edited form as:Neuroscience. 2007 July 13; 147(3): 674-679. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript . As a consequence, the identification of acrolein adducts has been proposed as a biologic marker for oxidative stress (Kehrer and Biswal, 2000). Accordingly, acrolein levels have been found increased in pathological conditions associated with oxidative stress, such as spinal cord injury (Luo et al., 2005), diabetic nephropathy (Suzuki and Miyata, 1999) and Alzheimer's Disease (AD) (Markesbery and Lovell, 1998,Cal...

show abstract

Section: Discussionsupporting

confidence: 93%

Section: Slot Blots: Protein Carbonyl Measurementmentioning

confidence: 85%

Acrolein induces selective protein carbonylation in synaptosomes

et al. 2007

Self Cite

View full text Add to dashboard Cite

show abstract

“…Further research is needed to address these questions. Overall, the data presented here parallel physiological events that lead to more severe stages of neurodegeneration in diseases like Alzheimer and Parkinson (Aksenov et al, 2001;Tsang and Soong, 2003). Thus, our findings indicate that the bee may emerge as a valuable model in neurogerontological research.…”

Section: Discussionsupporting

confidence: 71%

Cellular senescence in honey bee brain is largely independent of chronological age

Seehuus

Krekling

Amdam

2006

Experimental Gerontology

View full text Add to dashboard Cite

Accumulation of oxidative stress-induced damage in brain tissue plays an important role in the pathogenesis of normal aging and neurodegenerative diseases. Neuronal oxidative damage typically increases with age in humans, and also in the invertebrate and vertebrate model species most commonly used in aging research. By use of quantitative immunohistochemistry and Western blot, we show that this aspect of brain senescence is largely decoupled from chronological age in the honey bee (Apis mellifera). The bee is a eusocial insect characterized by the presence of a reproductive queen caste and a caste of functionally sterile female workers that performs various alloparental tasks such as nursing and foraging. We studied patterns of oxidative nitration and carbonylation damage in the brain of worker bees that performed nurse tasks as 8-and 200-day-olds and foraging tasks as 20-and 200-day-olds. In addition, we examined 180-day-old diutinus bees, a stress-resistant temporal worker form that survives unfavorable periods. Our results indicate that nitration damage occurs only at low levels in vivo, but that a 60-kDa protein from honey bee brain is selectively nitrated by peroxynitrite in vitro. Oxidative carbonylation is present at varying levels in the visual and chemosensory neuropiles of worker bees, and this inter-individual variation is better explained by social role than by chronological age.

show abstract

“…Strong evidence implicates oxidative damage to proteins as well as cytoskeletal abnormalities in the pathogenesis of several neurodegenerative diseases including Alzheimer disease, Parkinson disease, and amyotrophic lateral sclerosis (1,2). Microtubules formed by reversible polymerization and depolymerization of tubulin, a heterodimer composed of similar 50 kDa ␣ and ␤ subunits, are key components of the neuronal cytoskeleton and are required for proper neuron function (3,4).…”

mentioning

confidence: 99%

Cysteine Oxidation of Tau and Microtubule-associated Protein-2 by Peroxynitrite

Landino

Skreslet

Alston

2004

Journal of Biological Chemistry

View full text Add to dashboard Cite

Alterations in the redox status of proteins have been implicated in the pathology of several neurodegenerative conditions including Alzheimer and Parkinson diseases. We report that peroxynitrite-and hydrogen peroxide-induced disulfides in the neuron-specific microtubule-associated proteins tau and microtubuleassociated protein-2 are substrates for the ubiquitous thioredoxin reductase system composed of thioredoxin reductase, human or Escherichia coli thioredoxin, and NADPH. Tau and microtubule-associated protein-2 cysteine oxidation and reduction were quantitated by monitoring the incorporation of 5-iodoacetamidofluorescein, a thiol-specific labeling reagent. Cysteine oxidation of tau and microtubule-associated protein-2 to disulfides altered the ability of the proteins to promote the assembly of microtubules from purified porcine tubulin. Treatment of tau and microtubule-associated protein-2 with either the thioredoxin reductase system or small molecule reductants fully restores the ability of the MAPs to promote microtubule assembly. Thus changes in the redox state of microtubule-associated proteins may regulate microtubule polymerization in vivo.Strong evidence implicates oxidative damage to proteins as well as cytoskeletal abnormalities in the pathogenesis of several neurodegenerative diseases including Alzheimer disease, Parkinson disease, and amyotrophic lateral sclerosis (1, 2). Microtubules formed by reversible polymerization and depolymerization of tubulin, a heterodimer composed of similar 50 kDa ␣ and ␤ subunits, are key components of the neuronal cytoskeleton and are required for proper neuron function (3, 4). In addition to tubulin, the neuron-specific microtubule-associated proteins (MAPs), 1 MAP2 and tau, play a vital role in promoting and maintaining the neuronal cytoskeleton (5).Given the abundance of tubulin, tau, and MAP2 and the critical function they play in neurons, we are interested in studying the interaction they have with reactive oxygen species including peroxynitrite anion (ONOO Ϫ ) and hydrogen peroxide (H 2 O 2 ). ONOO Ϫ , formed from the reaction of nitric oxide and superoxide, is a strong oxidant that can damage several amino acids in proteins (6, 7).Previously we showed that tubulin, with 20 free sulfhydryl groups, is readily oxidized by ONOO Ϫ , and the extent of tubulin cysteine oxidation rather than other types of ONOO Ϫ -induced damage, correlates well with inhibition of microtubule polymerization (8). Addition of disulfide reducing agents restores a significant portion of the polymerization activity that is lost following ONOO Ϫ addition. Recently we reported (9, 10) that intra-and inter-subunit tubulin disulfides are substrates for two endogenous protein reductase systems including the thioredoxin reductase system (TRS) and the glutaredoxin reductase system.

show abstract

Protein oxidation in the brain in Alzheimer's disease

Cited by 465 publications

References 52 publications

Acrolein induces selective protein carbonylation in synaptosomes

Acrolein induces selective protein carbonylation in synaptosomes

Cellular senescence in honey bee brain is largely independent of chronological age

Cysteine Oxidation of Tau and Microtubule-associated Protein-2 by Peroxynitrite

Contact Info

Product

Resources

About