In vivo protein targets for increased quinoprotein adduct formation in aged substantia nigra

Yu, Guohua; Liu, Huiyan; Zhou, Wei; Zhu, Xuewei; Yu, Chao; Wang, Na; Zhang, Yi; Ma, Ji; Zhao, Yulan; Yan, Xu; Liao, Lujian; Ji, Hong‐Fang; Yuan, Chonggang; Ma, Jiyan

doi:10.1016/j.expneurol.2015.04.019

Cited by 21 publications

(21 citation statements)

References 48 publications

(59 reference statements)

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“…Although the toxic effects of DA have long been recognized as due to protein modifications,l ittle progress has been made in understanding the molecular basis and structural consequences resulting from these modifications.A limitation for the analysis of specific DA modification sites is the lack of suitable tools.N ear-IR fluorescence has been recently introduced as am ethod for recognition of quinonemodified proteins, [99] but the technique does not clearly identify which sites are involved in the modifications.T he same limitation applies to in vivo identification of proteins targeted by quinone reactive species through nitroblue tetrazolium (NBT)/glycinate redox-cycling staining after two-dimensional SDS-polyacrylamide gel electrophoresis. [100] Antibodies for DAQ-modified proteins would be useful but are not currently available.Inaddition, protein dopamination usually leads to insoluble aggregates that are difficult to analyze with HPLC/MS technique because they require preliminary proteolytic treatments with digestive enzymes, which may not reach their cleavage sites within the heterogeneous aggregates.F or these reasons,a lthough several reports deal with the effect of DA or l-DOPAo nn euronal proteins as described below in this section, the type and sites of modification are often not unequivocally identified. The situation is more favorable when the effect of protein dopamination is studied in vitro at relatively short reaction times,w hen DA melanization of the protein sample is not extensive.…”

Section: Dopamine Modification Of Proteins and Peptidesmentioning

confidence: 99%

Dopamine, Oxidative Stress and Protein–Quinone Modifications in Parkinson's and Other Neurodegenerative Diseases

et al. 2019

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Dopamine (DA) is the most important catecholamine in the brain, as it is the most abundant and the precursor of other neurotransmitters. Degeneration of nigrostriatal neurons of substantia nigra pars compacta in Parkinson's disease represents the best‐studied link between DA neurotransmission and neuropathology. Catecholamines are reactive molecules that are handled through complex control and transport systems. Under normal conditions, small amounts of cytosolic DA are converted to neuromelanin in a stepwise process involving melanization of peptides and proteins. However, excessive cytosolic or extraneuronal DA can give rise to nonselective protein modifications. These reactions involve DA oxidation to quinone species and depend on the presence of redox‐active transition metal ions such as iron and copper. Other oxidized DA metabolites likely participate in post‐translational protein modification. Thus, protein–quinone modification is a heterogeneous process involving multiple DA‐derived residues that produce structural and conformational changes of proteins and can lead to aggregation and inactivation of the modified proteins.

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Section: Dopamine Modification Of Proteins and Peptidesmentioning

confidence: 99%

Dopamine, Oxidative Stress and Protein–Quinone Modifications in Parkinson's and Other Neurodegenerative Diseases

et al. 2019

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“…It is known that a large part of glucose molecules utilized by the brain is produced via gluconeogenesis. The altered activity of MDA is associated with Parkinson's disease [218], Alzheimer's disease [219], schizophrenia [220], and cancer [221, 222]. …”

Section: Oxidation Protein-adductsmentioning

confidence: 99%

Mitochondrial dysfunction and oxidative stress in aging and cancer

et al. 2016

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Aging and cancer are the most important issues to research. The population in the world is growing older, and the incidence of cancer increases with age. There is no doubt about the linkage between aging and cancer. However, the molecular mechanisms underlying this association are still unknown. Several lines of evidence suggest that the oxidative stress as a cause and/or consequence of the mitochondrial dysfunction is one of the main drivers of these processes. Increasing ROS levels and products of the oxidative stress, which occur in aging and age-related disorders, were also found in cancer. This review focuses on the similarities between ageing-associated and cancer-associated oxidative stress and mitochondrial dysfunction as their common phenotype.

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“…Das Gleiche gilt fürdie Invivo-Identifizierung von Proteinen, die von chinonreaktiven Verbindungen angegriffen werden, nach Färbung durch Nitroblautetrazolium(NBT)/Glycinat-Redoxzyklisierung nach zweidimensionaler SDS-Polyacrylamid-Gelelektrophorese. [100] Antikçrper für DAQ-modifizierte Proteine wären hilfreich, sind jedoch aktuell nicht verfügbar. Außerdem bilden sich bei Proteindopaminierungen meist unlçsliche Aggregate,d ie mit HPLC/MS-Techniken schwer zu analysieren sind, weil sie zunächst mit proteolytischen Enzymen abgebaut werden müssen;d ie Spaltstellen in den heterogenen Aggregaten sind fürd ie Enzyme jedoch oft nicht zugänglich.…”

Section: Dopaminmodifikation Von Proteinen Und Peptidenunclassified

Dopamin, oxidativer Stress und Protein‐Chinonmodifikationen bei Parkinson und anderen neurodegenerativen Erkrankungen

Monzani¹,

Nicolis²,

Dell’Acqua³

et al. 2019

Angewandte Chemie

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Dopamin (DA) ist das wichtigste und häufigste Catecholamin im Gehirn und zugleich Vorläufer anderer Neurotransmitter. Die Degeneration von Neuronen des Nigrostriatums (Substantia nigra, Pars compacta) bei Parkinson‐Kranken ist die am besten untersuchte Verknüpfung zwischen Neurotransmission und Neuropathologie durch DA. Catecholamine sind reaktive Moleküle, für die es komplexe Kontroll‐ und Transportsysteme gibt. Unter normalen Bedingungen werden kleine Mengen cytosolischen Dopamins unter Melanisierung von Peptiden und Proteinen schrittweise zu Neuromelanin umgewandelt. Überschießendes cytosolisches oder extraneuronales DA kann allerdings unselektive Proteinmodifikationen auslösen. Die dabei ablaufende Oxidation von DA zu Chinonverbindungen hängt von der Gegenwart redoxaktiver Übergangsmetallionen wie Eisen und Kupfer ab. Auch andere oxidierte DA‐Metaboliten sind wahrscheinlich an posttranslationalen Proteinmodifikationen beteiligt. Die Protein‐Chinonmodifikation ist also ein heterogener Vorgang mit verschiedenen DA‐Abkömmlingen, die Struktur‐ und Konformationsänderungen von Proteinen hervorrufen; dies kann zur Aggregation und Inaktivierung der modifizierten Proteine führen.

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In vivo protein targets for increased quinoprotein adduct formation in aged substantia nigra

Cited by 21 publications

References 48 publications

Dopamine, Oxidative Stress and Protein–Quinone Modifications in Parkinson's and Other Neurodegenerative Diseases

Dopamine, Oxidative Stress and Protein–Quinone Modifications in Parkinson's and Other Neurodegenerative Diseases

Mitochondrial dysfunction and oxidative stress in aging and cancer

Dopamin, oxidativer Stress und Protein‐Chinonmodifikationen bei Parkinson und anderen neurodegenerativen Erkrankungen

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