l-Carnitine protects neurons from 1-methyl-4-phenylpyridinium-induced neuronal apoptosis in rat forebrain culture
Abstract
1-Methyl-4-phenylpyridinium ion (MPP+), an inhibitor of mitochondrial complex I, has been widely used as a neurotoxin because it elicits a severe Parkinson's disease-like syndrome with an elevation of intracellular reactive oxygen species (ROS) and apoptosis. L-carnitine plays an integral role in attenuating the brain injury associated with mitochondrial neurodegenerative disorders. The present study investigates the effects of L-carnitine against the toxicity of MPP+ in rat forebrain primary cultures. Cells in culture were treated for 24 h with 100, 250, 500 and 1000 microM MPP+ alone or co-incubated with L-carnitine. MPP+ produced a dose-related increase in DNA fragmentation as measured by cell death ELISA (enzyme-linked immunosorbent assay), an increase in the number of TUNEL (terminal dUTP nick-end labeling)-positive cells and a reduction in the mitochondrial metabolism of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). No significant effect was observed with the release of lactate dehydrogenase (LDH), indicating that cell death presumably occurred via apoptotic mechanisms. Co-incubation of MPP+ with L-carnitine significantly reduced MPP+-induced apoptosis. Western blot analyses showed that neurotoxic concentrations of MPP+ decreased the ratio of BCL-X(L) to Bax and decreased the protein levels of polysialic acid neural cell adhesion molecules (PSA-NCAM), a neuron specific marker. L-carnitine blocked these effects of MPP+ suggesting its potential therapeutic utility in degenerative disorders such as Parkinson's disease, Alzheimer's disease, ornithine transcarbamylase deficiency and other mitochondrial diseases.
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Carnitine and β-hydroxybutyrate has shown to protect against MPTP toxicity.
“Carnitine and β-hydroxybutyrate has shown to protect against MPTP toxicity189-191.”
From Mitochondrial Approaches for Neuroprotection (2008) · cites this paper as [190]
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Mitochondrial Approaches for Neuroprotection
Chaturvedi, R. K., & Beal, M. F. (2008) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1427.027 · Cited by 294 · see citing works
- Authors
- Wang, C., Sadovova, N., Ali, H. K., Duhart, H. M., Fu, X., Zou, X., Patterson, T. A., Binienda, Z. K., Virmani, A., Paule, M. G., Slikker, W., & Ali, S. F.
- Affiliations
- National Center for Toxicological Research (US)
- Sigma Tau (Italy) (IT)
- Venue
- Neuroscience
- Publisher
- Elsevier BV
- Published
- 2007-01
- Volume
- 144
- Issue
- 1
- Pages
- 46-55
- ISSN
- 0306-4522 (ISSN-L)
- OpenAlex
- W2071468700
- Cited by
- 55
- References
- 48
- Citations by year
- 2026: 1 · 2025: 3 · 2021: 2 · 2020: 2 · 2019: 5 · 2018: 2 · 2017: 1 · 2016: 1 · 2015: 3 · 2014: 1 · 2013: 5 · 2012: 4
- FWCI
- 2.75
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Neuroscience › Neurology › Neurological Disorders and Treatments
- Keywords
- L-carnitine, MPP+, MPP+ neurotoxicity, neuronal apoptosis, Parkinson's disease, mitochondrial complex I inhibition, reactive oxygen species, PSA-NCAM, mitochondrial dysfunction, neuroprotection, forebrain neurons
- MeSH terms
- Animals, Carnitine, Cell Nucleus, Cells, Cultured, Dose-Response Relationship, Drug, Enzyme-Linked Immunosorbent Assay, Immunohistochemistry, L-Lactate Dehydrogenase, Neurons, Sialic Acids, Tetrazolium Salts, Thiazoles, Blotting, Western, 1-Methyl-4-phenylpyridinium, Prosencephalon, Rats, Sprague-Dawley, Apoptosis, Neuroprotective Agents, In Situ Nick-End Labeling, bcl-X Protein, bcl-2-Associated X Protein, Rats
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