1. Synergistic anti-Parkinsonism activity of high doses of B vitamins in a chronic cellular model.
- Author
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Jia H, Liu Z, Li X, Feng Z, Hao J, Li X, Shen W, Zhang H, and Liu J
- Subjects
- Biomarkers, Cell Line, Tumor, Coenzymes metabolism, Coenzymes pharmacology, Coenzymes therapeutic use, DNA Damage drug effects, DNA Damage physiology, Dose-Response Relationship, Drug, Drug Administration Schedule, Drug Synergism, Electron Transport Complex I drug effects, Electron Transport Complex I metabolism, Heat-Shock Proteins drug effects, Heat-Shock Proteins metabolism, Humans, Membrane Potential, Mitochondrial drug effects, Membrane Potential, Mitochondrial physiology, Mitochondria metabolism, Mitochondrial Diseases metabolism, Mitochondrial Diseases physiopathology, Models, Biological, Nerve Tissue Proteins drug effects, Nerve Tissue Proteins metabolism, Oxidative Stress physiology, Oxygen Consumption drug effects, Oxygen Consumption physiology, Parkinson Disease metabolism, Parkinson Disease physiopathology, Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Reactive Oxygen Species antagonists & inhibitors, Reactive Oxygen Species metabolism, Rotenone antagonists & inhibitors, Rotenone toxicity, Transcription Factors drug effects, Transcription Factors metabolism, Ubiquitin antagonists & inhibitors, Ubiquitin metabolism, Uncoupling Agents antagonists & inhibitors, Uncoupling Agents toxicity, Vitamin B Complex metabolism, Vitamin B Complex therapeutic use, alpha-Synuclein antagonists & inhibitors, alpha-Synuclein metabolism, Mitochondria drug effects, Mitochondrial Diseases drug therapy, Oxidative Stress drug effects, Parkinson Disease drug therapy, Vitamin B Complex pharmacology
- Abstract
We propose that elevation of mitochondrial enzyme cofactors may prevent or ameliorate neurodegenerative diseases by improving mitochondrial function. In the present study, we investigated the effects of high doses of B vitamins, the precursors of mitochondrial enzyme cofactors, on mitochondrial dysfunction, oxidative stress, and Parkinsonism in a 4-week long rotenone treatment-induced cellular model of Parkinson's disease (PD). Pretreatment with B vitamins (also 4 weeks) prevented rotenone-induced: (1) mitochondrial dysfunction, including reduced mitochondrial membrane potential and activities of complex I; (2) oxidative stress, including increase in reactive oxygen species, oxidative DNA damage and protein oxidation, and (3) Parkinsonism parameters, including accumulation of alpha-synuclein and poly-ubiquitin. The optimum doses were found around 2.5- and 5-fold of that in normal MEM medium. The 4-week pretreatment was chosen based on time-dependent experiments that pretreatments longer than 2 weeks resulted in a decrease in oxidants, an increase in oxygen consumption, and up-regulation of complex I activity and PGC-1alpha expression. Individual B vitamins at the same doses did not show a similar effect suggesting that these B vitamins work synergistically. These results suggest that administration of high doses of B vitamins sufficient to elevate mitochondrial enzyme cofactors may be effective in preventing PD by reducing oxidative stress and improving mitochondrial function., (Copyright (c) 2008 Elsevier Inc. All rights reserved.)
- Published
- 2010
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