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D-beta-hydroxybutyrate protects dopaminergic SH-SY5Y cells in a rotenone model of Parkinson's disease.
- Source :
-
Journal of neuroscience research [J Neurosci Res] 2006 Nov 01; Vol. 84 (6), pp. 1376-84. - Publication Year :
- 2006
-
Abstract
- It has been postulated that the pathogenesis of Parkinson's disease (PD) is associated with mitochondrial dysfunction. Rotenone, an inhibitor of mitochondrial complex I, provides models of PD both in vivo and in vitro. We investigated the neuroprotective effect of D-beta-hydroxybutyrate (bHB), a ketone body, against rotenone toxicity by using SH-SY5Y dopaminergic neuroblastoma cells. SH-SY5Y cells, differentiated by all-trans-retinoic acid, were exposed to rotenone at concentrations ranging from 0 to 1,000 nM. We evaluated cellular oxidation reduction by the alamarBlue assay, viability by lactate dehydrogenase (LDH) assay, and survival/death ratio by live/dead assays. Exposure to rotenone for 48 hr oxidized cells and decreased their viability and survival rate in a concentration-dependent manner. Pretreatment of cells with 8 mM bHB provided significant protection to SH-SY5Y cells. Whereas rotenone caused the loss of mitochondrial membrane potential, released cytochrome c into the cytosol, and reduced cytochrome c content in mitochondria, addition of bHB blocked this toxic effect. bHB also attenuated the rotenone-induced activation of caspase-9 and caspase-3. Administration of 0-10 mM 3-nitropropionic acid, a complex II inhibitor, also decreased the reducing power of SH-SY5Y cells measured by alamarBlue assay. Pretreatment with 8 mM bHB attenuated the decrease of alamarBlue fluorescence. These data demonstrated that bHB had a neuroprotective effect that supported the mitochondrial respiration system by reversing the inhibition of complex I or II. Ketone bodies, the alternative energy source in the mammalian brain, appear to have therapeutic potential in PD.<br /> (Copyright 2006 Wiley-Liss, Inc.)
- Subjects :
- Caspase 3 metabolism
Caspase 9 metabolism
Cell Line, Tumor
Cell Survival drug effects
Fluorescent Dyes
Humans
Indoles
Ketone Bodies metabolism
L-Lactate Dehydrogenase metabolism
Membrane Potentials drug effects
Neurotoxins toxicity
Nitro Compounds toxicity
Oxidation-Reduction
Parkinson Disease, Secondary pathology
Propionates toxicity
Succinates pharmacology
3-Hydroxybutyric Acid pharmacology
Dopamine physiology
Neurons pathology
Parkinson Disease, Secondary chemically induced
Parkinson Disease, Secondary prevention & control
Rotenone antagonists & inhibitors
Rotenone toxicity
Uncoupling Agents antagonists & inhibitors
Uncoupling Agents toxicity
Subjects
Details
- Language :
- English
- ISSN :
- 0360-4012
- Volume :
- 84
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Journal of neuroscience research
- Publication Type :
- Academic Journal
- Accession number :
- 16917840
- Full Text :
- https://doi.org/10.1002/jnr.21021