Individual Amino Acid Supplementation Can Improve Energy Metabolism and Decrease ROS Production in Neuronal Cells Overexpressing Alpha-Synuclein

Autor: Henry Gong, Sandra Zivkovic, Umesh K. Jinwal, Vinh B. Dinh, Dale Chaput, Devon Placides, Yumeng Zhang, Stanley M. Stevens, Eni Cvitkovic, Ernide Frederic, Vedad Delic, Tam-Anh Phan, Christian Reynes, Daniel C. Lee, Josean Cruz, Hamed Mirzaei, Jeddidiah W. D. Griffin, Patrick C. Bradshaw
Rok vydání: 2017
Předmět:
Paraquat
0301 basic medicine
Bioenergetics
animal diseases
Drug Evaluation
Preclinical
Oxidative phosphorylation
Mitochondrion
medicine.disease_cause
Neuroblastoma
03 medical and health sciences
Cellular and Molecular Neuroscience
chemistry.chemical_compound
Adenosine Triphosphate
Oxygen Consumption
0302 clinical medicine
Cell Line
Tumor
medicine
Humans
Citrate synthase
Ferrous Compounds
Amino Acids
Neurons
chemistry.chemical_classification
Reactive oxygen species
biology
Recombinant Proteins
Culture Media
Mitochondria
nervous system diseases
Citric acid cycle
Oxidative Stress
030104 developmental biology
nervous system
Neurology
chemistry
Biochemistry
alpha-Synuclein
biology.protein
Molecular Medicine
Energy Metabolism
Reactive Oxygen Species
Adenosine triphosphate
030217 neurology & neurosurgery
Oxidative stress
Zdroj: NeuroMolecular Medicine. 19:322-344
ISSN: 1559-1174
1535-1084
DOI: 10.1007/s12017-017-8448-8
Popis: Parkinson's disease (PD) is a neurodegenerative disorder characterized by alpha-synuclein accumulation and loss of dopaminergic neurons in the substantia nigra (SN) region of the brain. Increased levels of alpha-synuclein have been shown to result in loss of mitochondrial electron transport chain complex I activity leading to increased reactive oxygen species (ROS) production. WT alpha-synuclein was stably overexpressed in human BE(2)-M17 neuroblastoma cells resulting in increased levels of an alpha-synuclein multimer, but no increase in alpha-synuclein monomer levels. Oxygen consumption was decreased by alpha-synuclein overexpression, but ATP levels did not decrease and ROS levels did not increase. Treatment with ferrous sulfate, a ROS generator, resulted in decreased oxygen consumption in both control and alpha-synuclein overexpressing cells. However, this treatment only decreased ATP levels and increased ROS production in the cells overexpressing alpha-synuclein. Similarly, paraquat, another ROS generator, decreased ATP levels in the alpha-synuclein overexpressing cells, but not in the control cells, further demonstrating how alpha-synuclein sensitized the cells to oxidative insult. Proteomic analysis yielded molecular insights into the cellular adaptations to alpha-synuclein overexpression, such as the increased abundance of many mitochondrial proteins. Many amino acids and citric acid cycle intermediates and their ester forms were individually supplemented to the cells with L-serine, L-proline, L-aspartate, or L-glutamine decreasing ROS production in oxidatively stressed alpha-synuclein overexpressing cells, while diethyl oxaloacetate or L-valine supplementation increased ATP levels. These results suggest that dietary supplementation with individual metabolites could yield bioenergetic improvements in PD patients to delay loss of dopaminergic neurons.
Databáze: OpenAIRE
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