Increased Protein Oxidation in Human Substantia Nigra Pars Compacta in Comparison with Basal Ganglia and Prefrontal Cortex Measured with an Improved Dinitrophenylhydrazine Assay
Erik Floor,Mary G. Wetzel +1 more
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TLDR
Elevated oxidative stress is elevated in human substantia nigra pars compacta in comparison with other regions and that oxidative damage is higher within the dopaminergic neurons in aging and in Parkinson's disease.Abstract:
The dopaminergic phenotype of neurons in human substantia nigra deteriorates during normal aging, and loss of these neurons is prominent in Parkinson's disease. These degenerative processes are hypothesized to involve oxidative stress. To compare oxidative stress in the nigra and related regions, we measured carbonyl modifications of soluble proteins in postmortem samples of substantia nigra, basal ganglia, and prefrontal cortex from neurologically normal subjects, using an improved 2,4-dinitrophenylhydrazine assay. The protein carbonyl content was found to be about twofold higher in substantia nigra pars compacta than in the other regions. To further analyze this oxidative damage, the distribution of carbonyl groups on soluble proteins was determined by western immunoblot analysis. This method revealed that carbonyl content of the major proteins in each region was linearly dependent on molecular weight. This distribution raises the possibility that protein carbonyl content is controlled by a size-dependent mechanism in vivo. Our results suggest that oxidative stress is elevated in human substantia nigra pars compacta in comparison with other regions and that oxidative damage is higher within the dopaminergic neurons. Elevated oxidative damage may contribute to the degeneration of nigral dopaminergic neurons in aging and in Parkinson's disease.read more
Citations
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Journal ArticleDOI
Protein carbonyl groups as biomarkers of oxidative stress.
TL;DR: The usage of protein CO groups as biomarkers of oxidative stress has some advantages in comparison with the measurement of other oxidation products because of the relative early formation and the relative stability of carbonylated proteins.
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Oxidative stress in Parkinson's disease
TL;DR: Oxidative stress contributes to the cascade leading to dopamine cell degeneration in Parkinson's disease (PD), but oxidative stress is intimately linked to other components of the degenerative process, such as mitochondrial dysfunction, excitotoxicity, nitric oxide toxicity and inflammation.
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Free Radicals: Properties, Sources, Targets, and Their Implication in Various Diseases
TL;DR: The free radicals induced oxidative stress has been reported to be involved in several diseased conditions such as diabetes mellitus, neurodegenerative disorders, cardiovascular diseases, cardiovascular disease, respiratory diseases, cataract development, rheumatoid arthritis and in various cancers.
Journal ArticleDOI
The Role of Oxidative Stress in Parkinson’s Disease
TL;DR: Animal models of PD have yielded some insights into the molecular pathways of neuronal degeneration and highlighted previously unknown mechanisms by which oxidative stress contributes to PD, but therapeutic attempts to target the general state of oxidative stress in clinical trials have failed to demonstrate an impact on disease progression.
Journal ArticleDOI
Pathogenesis of Parkinson's disease: dopamine, vesicles and alpha-synuclein.
Julie Lotharius,Patrik Brundin +1 more
TL;DR: It is proposed that defective sequestration of dopamine into vesicles, leading to the generation of reactive oxygen species in the cytoplasm, is a key event in the demise of dopaminergic neurons in Parkinson's disease and might represent a common pathway that underlies both genetic and sporadic forms of the disorder.
References
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Book ChapterDOI
Determination of carbonyl content in oxidatively modified proteins.
Rodney L. Levine,Donita Garland,Cynthia N. Oliver,Adolfo Amici,Isabel Climent,Anke-G. Lenz,Bong-Whan Ahn,Shmuel Shaltiel,Earl R. Stadtman +8 more
TL;DR: This chapter discusses methods to determine carbonyl content in oxidatively modified proteins and quantitated protein-bound pyruvoyl groups through formation of a Schiff base with p-aminobenzoic acid followed by reduction with cyanoborohydride.
Journal ArticleDOI
Ageing and parkinson's disease: substantia nigra regional selectivity
Julian Fearnley,Andrew J. Lees +1 more
TL;DR: It is suggested that age-related attrition of pigmented nigral cells is not an important factor in the pathogenesis of Parkinson's disease and the regional selectivity of PD is relatively specific.
Journal ArticleDOI
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André Parent,Lili-Naz Hazrati +1 more
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