Species fractionation in a case-control study concerning Parkinson’s disease: Cu-amino acids discriminate CSF of PD from controls

Willkommen, Desiree; Lucio, Marianna; Schmitt‐Kopplin, Philippe; Gazzaz, Malaz; Schroeter, Michael; Sigaroudi, Ali; Michalke, Bernhard

doi:10.1016/j.jtemb.2018.01.005

Cited by 24 publications

(18 citation statements)

References 59 publications

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“…A change of associated transition metal to the metabolites could be an amplifying factor for increased oxidative stress in PD and also for mitochondrial dysfunction. A dysregulation of the metals iron, copper, manganese, and zinc was already found within these sample-set [65]. Thereby a dysregulation of specific ratios between different mass fractions of these metals were found to be significantly different in PD and controls.…”

Section: Discussionmentioning

confidence: 62%

Metabolomic investigations in cerebrospinal fluid of Parkinson's disease

et al. 2018

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The underlying mechanisms of Parkinson´s disease are not completely revealed. Especially, early diagnostic biomarkers are lacking. To characterize early pathophysiological events, research is focusing on metabolomics. In this case-control study we investigated the metabolic profile of 31 Parkinson´s disease-patients in comparison to 95 neurologically healthy controls. The investigation of metabolites in CSF was performed by a 12 Tesla SolariX Fourier transform-ion cyclotron resonance-mass spectrometer (FT-ICR-MS). Multivariate statistical analysis sorted the most important biomarkers in relation to their ability to differentiate Parkinson versus control. The affected metabolites, their connection and their conversion pathways are described by means of network analysis. The metabolic profiling by FT-ICR-MS in CSF yielded in a good group separation, giving insights into the disease mechanisms. A total number of 243 metabolites showed an affected intensity in Parkinson´s disease, whereas 15 of these metabolites seem to be the main biological contributors. The network analysis showed a connection to the tricarboxylic cycle (TCA cycle) and therefore to mitochondrial dysfunction and increased oxidative stress within mitochondria. The metabolomic analysis of CSF in Parkinson´s disease showed an association to pathways which are involved in lipid/ fatty acid metabolism, energy metabolism, glutathione metabolism and mitochondrial dysfunction.

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Section: Discussionmentioning

confidence: 62%

Metabolomic investigations in cerebrospinal fluid of Parkinson's disease

et al. 2018

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“…In the work by Gorell and coworkers, association of Parkinson disease with copper or manganese and combinations of mixtures containing lead, iron and copper were proved (102,103). The potentiation between copper and iron in Parkinson disease patients was proved in cerebrospinal fl uid as well (104). Another study reported that number of copper ions bound on one molecule of ceruloplasmin was reduced in patients suffering from Parkinson disease (105).…”

Section: Alzheimer Disease and The Other Neurodegenerationsmentioning

confidence: 94%

Copper and copper nanoparticles toxicity and their impact on basic functions in the body

Pohanka¹

2019

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Copper is a biogenic metal having multiple functions in basic processes in organisms and it is common in all kingdoms of life. Limited intake of copper is a problem; however, doses of copper exceeding the recommended alimentary source are problematic as well and toxicity is soon manifested. Impact of copper nanoparticles on human health is another serious issue taken into consideration in this review. Regarding to copper toxicity, neurodegenerative disorders including Alzheimer and Parkinson diseases are suspected to be linked to copper toxicity or copper can contribute to their progression. Wilson and Menke diseases are also described as examples of copper intolerance. This paper is focused on the description, literature survey and discussion of the current knowledge about copper and copper nanoparticles toxicity and their involvement in various pathological processes (Tab. 6, Fig. 2, Ref. 171).

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“…CSF samples were taken from parallel running experiments detailed in Willkommen et al (2018). In brief, CSF samples were taken by standardized lumbar puncture at Cologne University Hospital.…”

Section: Methodsmentioning

confidence: 99%

“…Chemical speciation analysis is a well-established tool to study the biological role and metabolism of trace elements in general (Michalke et al, 2009; Vinceti et al, 2013) as well in neurodegeneration (Michalke et al, 2007b; Fernsebner et al, 2014; Neth, 2015; Neth et al, 2015; Venkataramani et al, 2018; Willkommen et al, 2018). In our previous study, we revealed that liquid chromatography-coupled-to-inductively-coupled plasma mass spectrometry (LC-ICP-MS) represents a suitable Fe(II)/Fe(III) speciation analysis method that provides good figures of merit using only 8–10 min analysis time per sample (Solovyev et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Iron Redox Speciation Analysis Using Capillary Electrophoresis Coupled to Inductively Coupled Plasma Mass Spectrometry (CE-ICP-MS)

2019

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Neuronal iron dyshomeostasis occurs in multiple neurodegenerative diseases. Changes in the Fe(II)/Fe(III) ratio toward Fe(II) is closely related to oxidative stress, lipid peroxidation, and represents a hallmark feature of ferroptosis. In particular for body fluids, like cerebrospinal fluid (CSF), reliable quantitative methods for Fe(II)/(III) redox-speciation analysis are needed to better assess the risk of Fe(II)-mediated damage in brain tissue. Currently in the field of metallomics, the most direct method to analyze both iron species is via LC-ICP-MS. However, this Fe(II)/(III) speciation analysis method suffers from several limitations. Here, we describe a unique method using capillary electrophoresis (CE)-ICP-MS for quantitative Fe(II)/(III) speciation analysis that can be applied for cell lysates and biofluid samples. Compared to LC, CE offers various advantages: (1) Capillaries have no stationary phase and do not depend on batch identity of stationary phases; (2) Replacement of aged or blocked capillaries is quick with no performance change; (3) Purge steps are effective and short; (4) Short sample analysis time. The final method employed 20 mM HCl as background electrolyte and a separation voltage of +25 kV. In contrary to the LC-method, no complexation of Fe-species with pyridine dicarboxylic acid (PDCA) was applied, since it hampered separation. Peak shapes and concentration detection limits were improved by combined conductivity-pH-stacking achieving 3 μg/L detection limit (3σ) at 13 nL injection volume. Calibrations from LOD—150 μg/L were linear [r2[Fe(II)] = 0.9999, r2[Fe(III)] = 0.9951]. At higher concentrations Fe(II) curve flattened significantly. Measurement precision was 3.5% [Fe(II) at 62 μg/L] or 2.2% [Fe(III) at 112 μg/L] and migration time precision was 2% for Fe(III) and 3% for Fe(II), each determined in 1:2 diluted lysates of human neuroblastoma cells. Concentration determination accuracy was checked by parallel measurements of SH-SY5Y cell lysates with validated LC-ICP-MS method and by recovery experiments after standard addition. Accuracy (n = 6) was 97.6 ± 3.7% Fe(III) and 105 ± 6.6%Fe(II). Recovery [(a) +33 μg/L or (b) +500 μg/L, addition per species] was (a): 97.2 ± 13% [Fe(II)], 108 ± 15% [Fe(III)], 102.5 ± 7% (sum of species), and (b) 99±4% [Fe(II)], 101 ± 6% [Fe(III)], 100 ± 5% (sum of species). Migration time shifts in CSF samples were due to high salinity, but both Fe-species were identified by standard addition.

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Species fractionation in a case-control study concerning Parkinson’s disease: Cu-amino acids discriminate CSF of PD from controls

Cited by 24 publications

References 59 publications

Metabolomic investigations in cerebrospinal fluid of Parkinson's disease

Metabolomic investigations in cerebrospinal fluid of Parkinson's disease

Copper and copper nanoparticles toxicity and their impact on basic functions in the body

Iron Redox Speciation Analysis Using Capillary Electrophoresis Coupled to Inductively Coupled Plasma Mass Spectrometry (CE-ICP-MS)

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