P2–139: Oxidation of cerebrospinal fluid proteins in aging and Alzheimer's disease

Korolainen, Minna A.; Nyman, Tuula A.; Nyyssönen, Paula; Hartikainen, Samuel; Pirttilä, Tuula

doi:10.1016/j.jalz.2006.05.977

Cited by 4 publications

(5 citation statements)

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“…Supported by the correlation of AD symptoms with downregulation of L‐PGDS concentration in the CSF of AD brain, we posit that L‐PGDS targets Aβ in AD mouse brain with high turnover suggestive of fast kinetic binding. [ 56–58 ] The proximity of the hippocampus to the ventricles could be the reason for the increase in intensity after 48 h, indicating that these conjugates can sequester out of the brain through the CSF. AD‐associated anatomical changes are known to progress from the entorhinal cortex to other cortical regions via the hippocampus.…”

Section: Discussionmentioning

confidence: 99%

Lipocalin‐Type Prostaglandin d Synthase Conjugates as Magnetic Resonance Imaging Contrast Agents for Detecting Amyloid β‐Rich Regions in the Brain of Live Alzheimer's Disease Mice

Sharma

Grandjean

Phillips

et al. 2021

Advanced NanoBiomed Research

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With a significant proportion of the global population growing older (>60 years), the low success rates of current diagnoses for early neurodegeneration signs are disappointing. Early detection of Alzheimer's disease (AD) can improve acclimatization and quality of life for patients in their later years. Endogenous proteins, such as the most abundant secreted protein in cerebrospinal fluid, lipocalin‐type prostaglandin d synthase (L‐PGDS), can bind the early toxic oligomers of amyloid β (Aβ) peptides implicated in AD and prevent their aggregation. Herein, the utility of L‐PGDS for detection of amyloids is demonstrated. L‐PGDS is conjugated with different iron‐oxide magnetic nanoparticles for contrast‐enhanced visualization using magnetic resonance imaging (MRI). These conjugates inhibit amyloid aggregation in vitro and improve viability in neuronal cells incubated with amyloid fibrils, showing a potential neuroprotective function. L‐PGDS‐ferritin conjugates, when administered intraventricularly, localize to AD‐associated amyloid‐rich regions in mice brain imaged using MRI and histological stains. As a proof‐of‐concept, it is demonstrated that L‐PGDS conjugates could reach the brain regions through non‐invasive intranasal administration. These conjugates are developed as the first entirely protein‐based nanoprobes for early detection of brain amyloids. The results of this study open a wider avenue for study of endogenous proteins as potential theranostics for AD.

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Section: Discussionmentioning

confidence: 99%

Lipocalin‐Type Prostaglandin d Synthase Conjugates as Magnetic Resonance Imaging Contrast Agents for Detecting Amyloid β‐Rich Regions in the Brain of Live Alzheimer's Disease Mice

Sharma

Grandjean

Phillips

et al. 2021

Advanced NanoBiomed Research

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“…After focusing MS-preparative IPG strips were equilibrated for 12 min in 6 M urea, 30% glycerol, 2% Sodium Dodecyl Following the incubation enabling protein-bound carbonyls derivatization, marked IPG strips were washed with 6 M Urea, 20% Glycerol, 1% SDS, 150 mM Tris-HCl pH 6.8. Marked IPG strips were then prepared for the second dimension, 39,40 followed by protein blotting to a PVDF membrane as described previously. 41 Next, PVDF membranes incubated overnight at 4 1C for immunostaining with the primary antibody solution, consisting of a 1 : 10.000 dilution of the anti-DNP IgG antibody (Sigma) in the Phosphate-buffered saline (PBS) containing 3.0% non-fat dry milk.…”

Section: Two-dimensional Polyacrylamide Gel Electrophoresismentioning

confidence: 99%

Plasma proteincarbonylation and physical exercise

et al. 2011

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Regular physical activity is associated with a reduced risk of coronary heart disease, as it probably modifies the balance between free-radical generation and antioxidant activity. On the other hand, however, acute physical activity increases oxygen uptake and leads to a temporary imbalance between the production of reactive oxygen and nitrogen species (RONS) and their disposal: this phenomenon is called oxidative stress. Proteins are one of the most important oxidation targets during physical exercise and carbonylation is one of the most common oxidative protein modifications. In cells there is a physiological level of oxidized proteins that doesn't interfere with cell function; however, an increase in oxidized protein levels may cause a series of cellular malfunctions that could lead to a disease state. For this reason the quantification of protein oxidation is important to distinguish a healthy state from a disease state. Several studies have demonstrated an increase of carbonylated plasma proteins in athletes after exercise, but none have identified targets of this oxidation. Recently a process of protein decarbonylation has been discovered, this may indicate that carbonylation could be involved in signal transduction. The aim of our research was to characterize plasma protein carbonylation in response to physical exercise in trained male endurance athletes. We analyzed by proteomic approach their plasma proteins at resting condition and after two different kinds of physical exercise (PE). We used 2D-GE followed by western blot with specific antibodies against carbonylated proteins. The 2D analysis identified Haptoglobin as potential protein target of carbonylation after PE. We also identified Serotransferrin and Fibrinogen whose carbonylation is reduced after exercise. These methods have allowed us to obtain an overview of plasma protein oxidation after physical exercise.

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“…13,14 Detection of protein carbonyl formation has been widely applied to the studies of various diseases and oxidative stress, and to the identification of markers of protein oxidation and diseases. 15,16 In the present study, we sought to further understand the effects of propiconazole on oxidative stress in mouse liver, especially on the oxidative stress-induced protein damage, and their potential roles in hepatotoxicity. As the first step, we analyzed overall status of oxidative stress and protein oxidation in mice exposed to propiconazole at a dose that had been shown to induce hepatic cancer in long-term chronic studies.…”

Section: Introductionmentioning

confidence: 99%

“…With the recent availability of techniques such as 2-DE, immunoblotting, and mass spectrometry (MS), the identification of carbonylated proteins has become possible. Identification of carbonylation of several proteins including beta-tubulin and creatine kinase has been reported. , Detection of protein carbonyl formation has been widely applied to the studies of various diseases and oxidative stress, and to the identification of markers of protein oxidation and diseases. , …”

Section: Introductionmentioning

confidence: 99%

Protein Carbonyl Formation in Response to Propiconazole-Induced Oxidative Stress

et al. 2009

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Propiconazole, a widely used fungicide, is hepatotoxic and hepatotumorigenic in mice. Previous genomic analysis of liver tissues from propiconazole-treated mice identified genes and pathways involved in oxidative stress, suggesting that oxidative stress may play a role in propiconazole-induced toxicity. To understand the contribution of oxidative stress on toxicity at the protein level, we developed an integrated approach for the systematic measurement of protein oxidation in the livers from propiconazole-treated mice. Liver protein carbonylation increased significantly after treatment with propiconazole, demonstrating propiconazole-associated induction of oxidative stress. Utilizing two-dimensional gel electrophoresis (2-DE), immunoblotting, and mass spectrometry, we identified 17 carbonylated proteins that were altered with varying intensities by propiconazole treatment. The potential effects of protein carbonylation on protein functions and cellular activities in the liver of propiconazole-treated mice were further investigated. A significant negative correlation between protein carbonylation and cytochrome c reductase activity was found. We conclude that glycolysis, mitochondrial respiratory chain, ATP production, amino acid metabolism, CO2 hydration, cellular antioxidant defense and detoxification system, and tetrahydrobiopterin pathways are affected by oxygen radicals in the livers of propiconazole-treated mice. This study suggests a mode of propiconazole-induced toxicity in mouse liver which primarily involves oxidative damage to cellular proteins.

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P2–139: Oxidation of cerebrospinal fluid proteins in aging and Alzheimer's disease

Cited by 4 publications

References 0 publications

Lipocalin‐Type Prostaglandin d Synthase Conjugates as Magnetic Resonance Imaging Contrast Agents for Detecting Amyloid β‐Rich Regions in the Brain of Live Alzheimer's Disease Mice

Lipocalin‐Type Prostaglandin d Synthase Conjugates as Magnetic Resonance Imaging Contrast Agents for Detecting Amyloid β‐Rich Regions in the Brain of Live Alzheimer's Disease Mice

Plasma proteincarbonylation and physical exercise

Protein Carbonyl Formation in Response to Propiconazole-Induced Oxidative Stress

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