Synergistic anti-Parkinsonism activity of high doses of B vitamins in a chronic cellular model.

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.

• Authors: Haiqun Jia, Zhongbo Liu, Xin Li, Zhihui Feng, Jiejie Hao, Xuesen Li, Weili Shen, Hongyu Zhang, Jiankang Liu
• Journal: Neurobiology of aging (Neurobiol Aging) Vol. 31 Issue 4 Pg. 636-46 (Apr 2010) ISSN: 1558-1497 [Electronic] United States
• PMID: 18639366 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright (c) 2008 Elsevier Inc. All rights reserved.

Chemical References

• Biomarkers
• Coenzymes
• Heat-Shock Proteins
• Nerve Tissue Proteins
• PPARGC1A protein, human
• Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
• Reactive Oxygen Species
• Transcription Factors
• Ubiquitin
• Uncoupling Agents
• alpha-Synuclein
• Rotenone
• Vitamin B Complex
• Electron Transport Complex I

Topics

• Biomarkers
• Cell Line, Tumor
• Coenzymes (metabolism, pharmacology, therapeutic use)
• DNA Damage (drug effects, physiology)
• Dose-Response Relationship, Drug
• Drug Administration Schedule
• Drug Synergism
• Electron Transport Complex I (drug effects, metabolism)
• Heat-Shock Proteins (drug effects, metabolism)
• Humans
• Membrane Potential, Mitochondrial (drug effects, physiology)
• Mitochondria (drug effects, metabolism)
• Mitochondrial Diseases (drug therapy, metabolism, physiopathology)
• Models, Biological
• Nerve Tissue Proteins (drug effects, metabolism)
• Oxidative Stress (drug effects, physiology)
• Oxygen Consumption (drug effects, physiology)
• Parkinson Disease (drug therapy, metabolism, physiopathology)
• Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
• Reactive Oxygen Species (antagonists & inhibitors, metabolism)
• Rotenone (antagonists & inhibitors, toxicity)
• Transcription Factors (drug effects, metabolism)
• Ubiquitin (antagonists & inhibitors, metabolism)
• Uncoupling Agents (antagonists & inhibitors, toxicity)
• Vitamin B Complex (metabolism, pharmacology, therapeutic use)
• alpha-Synuclein (antagonists & inhibitors, metabolism)