Journal
NEUROBIOLOGY OF AGING
Volume 31, Issue 4, Pages 636-646Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2008.05.031
Keywords
Mitochondrial membrane potential; Complex I; Reactive oxygen species; Oxidative DNA damage; Protein carbonyl
Categories
Funding
- National Institute on Aging [AG023265-01]
- Shanghai Science and Technical Committee [04DZ14007]
- Chinese Academy of Sciences [05PG14104]
- Zhejiang Hi-Sun Pharmaceuticals, Inc
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We propose that elevation of mitochondrial enzyme cofactors may prevent or ameliorate neurodegenerative diseases by improving mitochondria! 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-1 alpha 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. (C) 2008 Elsevier Inc All rights reserved
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