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Clavulanic acid inhibits MPP+-induced ROS generation and subsequent loss of dopaminergic cells
- Source :
- Brain Research. 1469:129-135
- Publication Year :
- 2012
- Publisher :
- Elsevier BV, 2012.
-
Abstract
- Clavulanic acid is a psychoactive compound that has been shown to modulate central nervous system activity. Importantly, in neurotoxin-induced animal models, clavulanic acid has been shown to improve motor function (Huh et al., 2010) suggesting that it can be neuroprotective; however, the mechanism as how clavulanic acid can induce neuroprotection is not known. We demonstrate here that clavulanic acid abrogates the effects of the neurotoxin 1-methyl-4-phenylpyridinium (MPP(+)) which mimics Parkinson's disease (PD) by inducing neurodegeneration. To further establish the mechanism we identified that clavulanic acid inhibits neurotoxin-induced loss of mitochondrial membrane potential and ROS production. Consistent with these results, neurotoxin-induced increase in Bax levels was also decreased in clavulanic acid treated cells. Importantly, neurotoxin-induced release of cytochrome c levels as well as caspase activation was also inhibited in clavulanic acid treated cells. In addition, Bcl-xl levels were also restored and the Bcl-xl/Bax ratio that is critical for inducing apoptosis was increased in clavulanic acid treated cells. Overall, these results suggest that clavulanic acid is intimately involved in inhibiting neurotoxin-induced loss of mitochondrial function and induction of apoptosis that contributes towards neuronal survival.
- Subjects :
- 1-Methyl-4-phenylpyridinium
Dopamine
Apoptosis
Caspase 3
Pharmacology
Neuroprotection
Article
chemistry.chemical_compound
Bcl-2-associated X protein
Cell Line, Tumor
Clavulanic acid
medicine
Humans
Molecular Biology
Clavulanic Acid
bcl-2-Associated X Protein
Membrane Potential, Mitochondrial
Neurons
biology
General Neuroscience
Cytochrome c
MPTP
Cytochromes c
Caspase 9
Mitochondria
Neuroprotective Agents
chemistry
biology.protein
Neurology (clinical)
Reactive Oxygen Species
Developmental Biology
medicine.drug
Subjects
Details
- ISSN :
- 00068993
- Volume :
- 1469
- Database :
- OpenAIRE
- Journal :
- Brain Research
- Accession number :
- edsair.doi.dedup.....8fd720629983587b6e8bf068f2f9daec